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1

Shirai, Y., K. Kashiwagi, N. Sakai, and N. Saito. "Phospholipase A(2) and its products are involved in the purinergic receptor-mediated translocation of protein kinase C in CHO-K1 cells." Journal of Cell Science 113, no. 8 (2000): 1335–43. http://dx.doi.org/10.1242/jcs.113.8.1335.

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The signal transduction involved in the purinergic stimuli-induced activation of protein kinase C (PKC) in CHO-K1 cells was investigated. Purinergic stimuli such as adenosine triphosphate and uridine triphosphate induced a transient translocation of PKC epsilon, gamma, and delta from the cytoplasm to the plasma membrane. These translocations were blocked by an inhibitor of phosphatidylinositol-specific phospholipase C (PLC), but not by an inhibitor of phosphatidylcholine-specific PLC. A diacylglycerol (DAG) analogue also induced reversible translocations of PKC gamma, epsilon, and delta from t
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2

Spek, Annabel, Bingsheng Li, Beata Rutz, et al. "Purinergic smooth muscle contractions in the human prostate: estimation of relevance and characterization of different agonists." Naunyn-Schmiedeberg's Archives of Pharmacology 394, no. 6 (2021): 1113–31. http://dx.doi.org/10.1007/s00210-020-02044-4.

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AbstractNon-adrenergic prostate smooth muscle contractions may account for the limited effectiveness of α1-adrenoceptor antagonists, which are the first-line option for medical treatment of voiding symptoms suggestive of benign prostatic hyperplasia. In non-human prostates, purinergic agonists induce contractions reaching similar magnitudes as α1-adrenergic contractions. However, evidence for the human prostate is highly limited, and pointed to much weaker purinergic contractions. Here, we examined contractions of different purinergic agonists in human prostate tissues. Tissues were obtained f
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Klausen, Polina, Daria Semenova, Daria Kostina, Vladimir Uspenskiy, and Anna Malashicheva. "Purinergic Signaling in Pathologic Osteogenic Differentiation of Aortic Valve Interstitial Cells from Patients with Aortic Valve Calcification." Biomedicines 11, no. 2 (2023): 307. http://dx.doi.org/10.3390/biomedicines11020307.

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Purinergic signaling is associated with a vast spectrum of physiological processes, including cardiovascular system function and, in particular, its pathological calcifications, such as aortic valve stenosis. Aortic valve stenosis (AS) is a degenerative disease for which there is no cure other than surgical replacement of the affected valve. Purinergic signaling is known to be involved in the pathologic osteogenic differentiation of valve interstitial cells (VIC) into osteoblast-like cells, which underlies the pathogenesis of AS. ATP, its metabolites and related nucleotides also act as signali
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Tingler, Anna, Charulekha Packirisamy, and Kristen Engevik. "EPITHELIAL PURINERGIC RECEPTORS ARE DOWNREGULATED IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE." Inflammatory Bowel Diseases 31, Supplement_1 (2025): S46. https://doi.org/10.1093/ibd/izae282.109.

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Abstract BACKGROUND Purines are among the most influential and ubiquitous signaling molecules. In the human body, there are 19 different purinergic receptor subtypes that are classified into P1 and P2 receptors. Several studies have revealed crucial roles for P2 purinergic receptors during inflammatory and infectious diseases experimentally using animal models. However, the distribution of P1 and P2 receptors in the human colon has not been fully mapped. Additionally, there is little information about changes in purinergic receptors in the setting of inflammatory bowel disease (IBD). We hypoth
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5

Zhang, Yong, and William G. Paterson. "Characterization of the peristaltic reflex in murine distal colon." Canadian Journal of Physiology and Pharmacology 94, no. 2 (2016): 190–98. http://dx.doi.org/10.1139/cjpp-2015-0086.

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Ascending and descending neuromuscular reflexes play an important role in gastrointestinal motility. However, the underlying mechanisms in colon are incompletely understood. Nerve stimulation (NS)- and balloon distention (BD)-mediated reflexes in distal colonic circular smooth muscle (CSM) and longitudinal smooth muscle (LSM) of mice were investigated using conventional intracellular recordings. In the CSM, NS evoked ascending purinergic inhibitory junction potentials (IJPs), whereas BD induced atropine-sensitive ascending depolarization with superimposed action potentials (APs). The ascending
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6

Guzman-Aranguez, Ana, Xavier Gasull, Yolanda Diebold, and Jesús Pintor. "Purinergic Receptors in Ocular Inflammation." Mediators of Inflammation 2014 (2014): 1–11. http://dx.doi.org/10.1155/2014/320906.

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Inflammation is a complex process that implies the interaction between cells and molecular mediators, which, when not properly “tuned,” can lead to disease. When inflammation affects the eye, it can produce severe disorders affecting the superficial and internal parts of the visual organ. The nucleoside adenosine and nucleotides including adenine mononucleotides like ADP and ATP and dinucleotides such as P1,P4-diadenosine tetraphosphate (Ap4A), and P1,P5-diadenosine pentaphosphate (Ap5A) are present in different ocular locations and therefore they may contribute/modulate inflammatory processes
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7

Chen, Zhiyong, Chi Zhang, Xiaodan Song, et al. "BzATP Activates Satellite Glial Cells and Increases the Excitability of Dorsal Root Ganglia Neurons In Vivo." Cells 11, no. 15 (2022): 2280. http://dx.doi.org/10.3390/cells11152280.

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The purinergic system plays an important role in pain transmission. Recent studies have suggested that activation of P2-purinergic receptors (P2Rs) may be involved in neuron-satellite glial cell (SGC) interactions in the dorsal root ganglia (DRG), but the details remain unclear. In DRG, P2X7R is selectively expressed in SGCs, which closely surround neurons, and is highly sensitive to 3’-O-(4-Benzoyl) benzoyl-ATP (BzATP). Using calcium imaging in intact mice to survey a large number of DRG neurons and SGCs, we examined how intra-ganglionic purinergic signaling initiated by BzATP affects neurona
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8

Muñoz, Manuel F., Theanne N. Griffith, and Jorge E. Contreras. "Mechanisms of ATP release in pain: role of pannexin and connexin channels." Purinergic Signalling 17, no. 4 (2021): 549–61. http://dx.doi.org/10.1007/s11302-021-09822-6.

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AbstractPain is a physiological response to bodily damage and serves as a warning of potential threat. Pain can also transform from an acute response to noxious stimuli to a chronic condition with notable emotional and psychological components that requires treatment. Indeed, the management of chronic pain is currently an important unmet societal need. Several reports have implicated the release of the neurotransmitter adenosine triphosphate (ATP) and subsequent activation of purinergic receptors in distinct pain etiologies. Purinergic receptors are broadly expressed in peripheral neurons and
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9

Scarpellino, Giorgia, Tullio Genova, Daniele Avanzato, et al. "Purinergic Calcium Signals in Tumor-Derived Endothelium." Cancers 11, no. 6 (2019): 766. http://dx.doi.org/10.3390/cancers11060766.

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Tumor microenvironment is particularly enriched with extracellular ATP (eATP), but conflicting evidence has been provided on its functional effects on tumor growth and vascular remodeling. We have previously shown that high eATP concentrations exert a strong anti-migratory, antiangiogenic and normalizing activity on human tumor-derived endothelial cells (TECs). Since both metabotropic and ionotropic purinergic receptors trigger cytosolic calcium increase ([Ca2+]c), the present work investigated the properties of [Ca2+]c events elicited by high eATP in TECs and their role in anti-migratory acti
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10

Scarpellino, Giorgia, Tullio Genova, Elisa Quarta, et al. "P2X Purinergic Receptors Are Multisensory Detectors for Micro-Environmental Stimuli That Control Migration of Tumoral Endothelium." Cancers 14, no. 11 (2022): 2743. http://dx.doi.org/10.3390/cancers14112743.

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The tumoral microenvironment often displays peculiar features, including accumulation of extracellular ATP, hypoxia, low pH-acidosis, as well as an imbalance in zinc (Zn2+) and calcium (Ca2+). We previously reported the ability of some purinergic agonists to exert an anti-migratory activity on tumor-derived human endothelial cells (TEC) only when applied at a high concentration. They also trigger calcium signals associated with release from intracellular stores and calcium entry from the external medium. Here, we provide evidence that high concentrations of BzATP (100 µM), a potent agonist of
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11

Dahl, Gerhard. "ATP release through pannexon channels." Philosophical Transactions of the Royal Society B: Biological Sciences 370, no. 1672 (2015): 20140191. http://dx.doi.org/10.1098/rstb.2014.0191.

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Extracellular adenosine triphosphate (ATP) serves as a signal for diverse physiological functions, including spread of calcium waves between astrocytes, control of vascular oxygen supply and control of ciliary beat in the airways. ATP can be released from cells by various mechanisms. This review focuses on channel-mediated ATP release and its main enabler, Pannexin1 (Panx1). Six subunits of Panx1 form a plasma membrane channel termed ‘pannexon’. Depending on the mode of stimulation, the pannexon has large conductance (500 pS) and unselective permeability to molecules less than 1.5 kD or is a s
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12

Boncoeur, Émilie, Guillaume F. Bouvet, Francis Migneault та ін. "Induction of nitric oxide synthase expression by lipopolysaccharide is mediated by calcium-dependent PKCα-β1 in alveolar epithelial cells". American Journal of Physiology-Lung Cellular and Molecular Physiology 305, № 2 (2013): L175—L184. http://dx.doi.org/10.1152/ajplung.00295.2012.

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Nitric oxide (NO) plays an important role in innate host defense and inflammation. In response to infection, NO is generated by inducible nitric oxide synthase (iNOS), a gene product whose expression is highly modulated by different stimuli, including lipopolysaccharide (LPS) from gram-negative bacteria. We reported recently that LPS from Pseudomonas aeruginosa altered Na+ transport in alveolar epithelial cells via a suramin-dependent process, indicating that LPS activated a purinergic response in these cells. To further study this question, in the present work, we tested whether iNOS mRNA and
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Buchanan, Kelly L., Laura E. Rupprecht, M. Maya Kaelberer, et al. "The preference for sugar over sweetener depends on a gut sensor cell." Nature Neuroscience 25, no. 2 (2022): 191–200. http://dx.doi.org/10.1038/s41593-021-00982-7.

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AbstractGuided by gut sensory cues, humans and animals prefer nutritive sugars over non-caloric sweeteners, but how the gut steers such preferences remains unknown. In the intestine, neuropod cells synapse with vagal neurons to convey sugar stimuli to the brain within seconds. Here, we found that cholecystokinin (CCK)-labeled duodenal neuropod cells differentiate and transduce luminal stimuli from sweeteners and sugars to the vagus nerve using sweet taste receptors and sodium glucose transporters. The two stimulus types elicited distinct neural pathways: while sweetener stimulated purinergic n
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14

Brayden, Joseph E., Yao Li, and Matthew J. Tavares. "Purinergic Receptors Regulate Myogenic Tone in Cerebral Parenchymal Arterioles." Journal of Cerebral Blood Flow & Metabolism 33, no. 2 (2012): 293–99. http://dx.doi.org/10.1038/jcbfm.2012.169.

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Myogenic tone is a fundamental aspect of vascular behavior in resistance arteries. This contractile response to changes in intravascular pressure is critically involved in blood flow autoregulation in tissues such as the brain, kidneys, and heart. Myogenic tone also helps regulate precapillary pressure and provides a level of background tone upon which vasodilator stimuli act to increase tissue perfusion when appropriate. Despite the importance of these processes in the brain, little is known about the mechanisms involved in control of myogenic tone in the cerebral microcirculation. Here, we r
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15

Yang, Lijing, Mengjia Hu, Yukai Lu, Songling Han, and Junping Wang. "Inflammasomes and the Maintenance of Hematopoietic Homeostasis: New Perspectives and Opportunities." Molecules 26, no. 2 (2021): 309. http://dx.doi.org/10.3390/molecules26020309.

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Hematopoietic stem cells (HSCs) regularly produce various blood cells throughout life via their self-renewal, proliferation, and differentiation abilities. Most HSCs remain quiescent in the bone marrow (BM) and respond in a timely manner to either physiological or pathological cues, but the underlying mechanisms remain to be further elucidated. In the past few years, accumulating evidence has highlighted an intermediate role of inflammasome activation in hematopoietic maintenance, post-hematopoietic transplantation complications, and senescence. As a cytosolic protein complex, the inflammasome
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Yang, Lijing, Mengjia Hu, Yukai Lu, Songling Han, and Junping Wang. "Inflammasomes and the Maintenance of Hematopoietic Homeostasis: New Perspectives and Opportunities." Molecules 26, no. 2 (2021): 309. http://dx.doi.org/10.3390/molecules26020309.

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Hematopoietic stem cells (HSCs) regularly produce various blood cells throughout life via their self-renewal, proliferation, and differentiation abilities. Most HSCs remain quiescent in the bone marrow (BM) and respond in a timely manner to either physiological or pathological cues, but the underlying mechanisms remain to be further elucidated. In the past few years, accumulating evidence has highlighted an intermediate role of inflammasome activation in hematopoietic maintenance, post-hematopoietic transplantation complications, and senescence. As a cytosolic protein complex, the inflammasome
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17

He, Jin-Rong, Shu-Guang Yu, Yong Tang, and Peter Illes. "Purinergic signaling as a basis of acupuncture-induced analgesia." Purinergic Signalling 16, no. 3 (2020): 297–304. http://dx.doi.org/10.1007/s11302-020-09708-z.

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Abstract This review summarizes experimental evidence indicating that purinergic mechanisms are causally involved in acupuncture (AP)-induced analgesia. Electroacupuncture (EAP) and manual AP release at pain-relevant acupoints ATP which may activate purinergic P2X receptors (Rs) especially of the P2X3 type situated at local sensory nerve endings (peripheral terminals of dorsal root ganglion [DRG] neurons); the central processes of these neurons are thought to inhibit via collaterals of ascending dorsal horn spinal cord neurons, pain-relevant pathways projecting to higher centers of the brain.
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18

Sangsiri, Sutheera, Hui Xu, Roxanne Fernandes, et al. "Spinal cord injury alters purinergic neurotransmission to mesenteric arteries in rats." American Journal of Physiology-Heart and Circulatory Physiology 318, no. 2 (2020): H223—H237. http://dx.doi.org/10.1152/ajpheart.00525.2019.

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Complications associated with spinal cord injury (SCI) result from unregulated reflexes below the lesion level. Understanding neurotransmission distal to the SCI could improve quality of life by mitigating complications. The long-term impact of SCI on neurovascular transmission is poorly understood, but reduced sympathetic activity below the site of SCI enhances arterial neurotransmission (1). We studied sympathetic neurovascular transmission using a rat model of long-term paraplegia (T2–3) and tetraplegia (C6–7). Sixteen weeks after SCI, T2–3 and C6–7 rats had lower blood pressure (BP) than s
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19

Bradley, Eamonn, Andrea Law, David Bell, and Christopher D. Johnson. "Effects of varying impulse number on cotransmitter contributions to sympathetic vasoconstriction in rat tail artery." American Journal of Physiology-Heart and Circulatory Physiology 284, no. 6 (2003): H2007—H2014. http://dx.doi.org/10.1152/ajpheart.01061.2002.

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We examined the contributions of the cotransmitters norepinephrine (NE), ATP, and neuropeptide Y (NPY) to sympathetically evoked vasoconstriction in the rat tail artery in isolated vascular rings by using 1–100 stimulation impulses at 20 Hz. Phentolamine (2 μM), the α-adrenoceptor antagonist, markedly reduced responses to all stimuli, although responses to lower impulse numbers were reduced less than responses to longer trains. The purinergic receptor antagonist suramin (100 μM) reduced all responses, but to a much greater extent with few impulse trains. Responses were further reduced or aboli
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20

Cabral-García, Guillermo A., José R. Cruz-Muñoz, Eduardo E. Valdez-Morales, Alma Barajas-Espinosa, Andrómeda Liñán-Rico, and Raquel Guerrero-Alba. "Pharmacology of P2X Receptors and Their Possible Therapeutic Potential in Obesity and Diabetes." Pharmaceuticals 17, no. 10 (2024): 1291. http://dx.doi.org/10.3390/ph17101291.

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The role of P2X ionotropic receptors in the behavior of purinergic signaling on pathophysiological processes has been widely studied. In recent years, the important participation of P2X receptors in physiological and pathological processes, such as energy metabolism, characteristic inflammatory responses of the immune system, and nociceptive activity in response to pain stimuli, has been noted. Here, we explore the molecular characteristics of the P2X receptors and the use of the different agonist and antagonist agents recently described, focusing on their potential as new therapeutic targets
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Iwanaga, Koichi, Takahisa Murata, Masatoshi Hori, and Hiroshi Ozaki. "Purinergic P2Y1 receptor signaling mediates wound stimuli-induced cyclooxygenase-2 expression in intestinal subepithelial myofibroblasts." European Journal of Pharmacology 702, no. 1-3 (2013): 158–64. http://dx.doi.org/10.1016/j.ejphar.2013.01.025.

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22

LIGHT, ALAN R., YING WU, RONALD W. HUGHEN, and PETER B. GUTHRIE. "Purinergic receptors activating rapid intracellular Ca2+ increases in microglia." Neuron Glia Biology 2, no. 2 (2005): 125–38. http://dx.doi.org/10.1017/s1740925x05000323.

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We provide both molecular and pharmacological evidence that the metabotropic, purinergic, P2Y6, P2Y12 and P2Y13 receptors and the ionotropic P2X4 receptor contribute strongly to the rapid calcium response caused by ATP and its analogues in mouse microglia. Real-time PCR demonstrates that the most prevalent P2 receptor in microglia is P2Y6 followed, in order, by P2X4, P2Y12, and P2X7 = P2Y13. Only very small quantities of mRNA for P2Y1, P2Y2, P2Y4, P2Y14, P2X3 and P2X5 were found. Dose-response curves of the rapid calcium response gave a potency order of: 2MeSADP>ADP=UDP=IDP=UTP>ATP>Bz
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23

Hanna, Ramy L., and Marc P. Kaufman. "Role played by purinergic receptors on muscle afferents in evoking the exercise pressor reflex." Journal of Applied Physiology 94, no. 4 (2003): 1437–45. http://dx.doi.org/10.1152/japplphysiol.01011.2002.

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The exercise pressor reflex is believed to be evoked, in part, by multiple metabolic stimuli that are generated when blood supply to exercising muscles is inadequate to meet metabolic demand. Recently, ATP, which is a P2 receptor agonist, has been suggested to be one of the metabolic stimuli evoking this reflex. We therefore tested the hypothesis that blockade of P2 receptors within contracting skeletal muscle attenuated the exercise pressor reflex in decerebrate cats. We found that popliteal arterial injection of pyridoxal phosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS; 10 mg/kg), a P2 re
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Saffioti, Nicolas Andres, Cora Lilia Alvarez, Zaher Bazzi, et al. "Dynamic recycling of extracellular ATP in human epithelial intestinal cells." PLOS Computational Biology 19, no. 6 (2023): e1011196. http://dx.doi.org/10.1371/journal.pcbi.1011196.

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Intestinal epithelial cells play important roles in the absorption of nutrients, secretion of electrolytes and food digestion. The function of these cells is strongly influenced by purinergic signalling activated by extracellular ATP (eATP) and other nucleotides. The activity of several ecto-enzymes determines the dynamic regulation of eATP. In pathological contexts, eATP may act as a danger signal controlling a variety of purinergic responses aimed at defending the organism from pathogens present in the intestinal lumen. In this study, we characterized the dynamics of eATP on polarised and no
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Henriques, Tiago, Emilio Agostinelli, Andres Hernandez-Clavijo, et al. "TMEM16A calcium-activated chloride currents in supporting cells of the mouse olfactory epithelium." Journal of General Physiology 151, no. 7 (2019): 954–66. http://dx.doi.org/10.1085/jgp.201812310.

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Glial-like supporting (or sustentacular) cells are important constituents of the olfactory epithelium that are involved in several physiological processes such as production of endocannabinoids, insulin, and ATP and regulation of the ionic composition of the mucus layer that covers the apical surface of the olfactory epithelium. Supporting cells express metabotropic P2Y purinergic receptors that generate ATP-induced Ca2+ signaling through the activation of a PLC-mediated cascade. Recently, we reported that a subpopulation of supporting cells expresses also the Ca2+-activated Cl− channel TMEM16
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Giannantoni, Antonella, Silvia Proietti, Silvia Giovannozzi, and Massimo Porena. "Vesical Urothelium and New Concepts." Urologia Journal 79, no. 1 (2012): 14–18. http://dx.doi.org/10.5301/ru.2012.9021.

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Vesical urothelium was long considered to simply be a protection barrier, which passively separates the urinary content from the underlying smooth muscle and the blood stream. Recent observations, though, have pointed out that vesical urothelium cells have clear active and sensory functions, in response to various physical and chemical stimuli. Among these characteristics are the expression of several neurotransmitters and receptors: Acetylcholine, Nitric Oxide, VIP, CGRP, NKA, SP and cholinergic, vanilloid, purinergic, and tachykinin receptors. Urothelium-produced neurotransmitters are likely
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27

Stauffer, Philip E., Jordon Brinkley, David A. Jacobson, Vito Quaranta, and Darren R. Tyson. "Purinergic Ca2+ Signaling as a Novel Mechanism of Drug Tolerance in BRAF-Mutant Melanoma." Cancers 16, no. 13 (2024): 2426. http://dx.doi.org/10.3390/cancers16132426.

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Drug tolerance is a major cause of relapse after cancer treatment. Despite intensive efforts, its molecular basis remains poorly understood, hampering actionable intervention. We report a previously unrecognized signaling mechanism supporting drug tolerance in BRAF-mutant melanoma treated with BRAF inhibitors that could be of general relevance to other cancers. Its key features are cell-intrinsic intracellular Ca2+ signaling initiated by P2X7 receptors (purinergic ligand-gated cation channels) and an enhanced ability for these Ca2+ signals to reactivate ERK1/2 in the drug-tolerant state. Extra
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Moschetta, Donato, Enrico Di Maria, Vincenza Valerio, et al. "Purinergic Receptor P2Y2 Stimulation Averts Aortic Valve Interstitial Cell Calcification and Myofibroblastic Activation." Biomedicines 10, no. 2 (2022): 457. http://dx.doi.org/10.3390/biomedicines10020457.

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Rationale—Calcific aortic valve stenosis (CAVS) is a pathological condition of the aortic valve with a prevalence of 3% in the general population. It is characterized by massive rearrangement of the extracellular matrix, mostly due to the accumulation of fibro-calcific deposits driven by valve interstitial cells (VIC), and no pharmacological treatment is currently available. The aim of this study was to evaluate the effects of P2Y2 receptor (P2RY2) activation on fibro-calcific remodeling of CAVS. Methods—We employed human primary VICs isolated from CAVS leaflets treated with 2-thiouridine-5′-t
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Oyasu, Miho, Mineko Fujimiya, Kaori Kashiwagi, Shiho Ohmori, Hirotsugu Imaeda та Naoaki Saito. "Immunogold Electron Microscopic Demonstration of Distinct Submembranous Localization of the Activated γPKC Depending on the Stimulation". Journal of Histochemistry & Cytochemistry 56, № 3 (2007): 253–65. http://dx.doi.org/10.1369/jhc.7a7291.2007.

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We examined the precise intracellular translocation of γ subtype of protein kinase C (γPKC) after various extracellular stimuli using confocal laser-scanning fluorescent microscopy (CLSM) and immunogold electron microscopy. By CLSM, treatment with 12- O-tetradecanoylphorbol-13-acetate (TPA) resulted in a slow and irreversible accumulation of green fluorescent protein (GFP)-tagged γPKC (γPKC–GFP) on the plasma membrane. In contrast, treatment with Ca2+ ionophore and activation of purinergic or NMDA receptors induced a rapid and transient membrane translocation of γPKC–GFP. Although each stimulu
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Khan, Amna, Salman Khan, and Yeong Shik Kim. "Insight into Pain Modulation: Nociceptors Sensitization and Therapeutic Targets." Current Drug Targets 20, no. 7 (2019): 775–88. http://dx.doi.org/10.2174/1389450120666190131114244.

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Pain is a complex multidimensional concept that facilitates the initiation of the signaling cascade in response to any noxious stimuli. Action potential generation in the peripheral nociceptor terminal and its transmission through various types of nociceptors corresponding to mechanical, chemical or thermal stimuli lead to the activation of receptors and further neuronal processing produces the sensation of pain. Numerous types of receptors are activated in pain sensation which vary in their signaling pathway. These signaling pathways can be regarded as a site for modulation of pain by targeti
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Murakami, Makoto, Yasuyuki Furukawa, and Shigetoshi Chiba. "Effects of Glibenclamide on Negative Cardiac Responses to Cholinergic and Purinergic Stimuli and Cromakalim in the Isolated Dog Heart." Japanese Journal of Pharmacology 65, no. 3 (1994): 215–22. http://dx.doi.org/10.1016/s0021-5198(19)35752-x.

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Murakami, Makoto, Yasuyuki Furukawa, and Shigetoshi Chiba. "Effects of Glibenclamide on Negative Cardiac Responses to Cholinerg and Purinergic Stimuli and Cromakalim in the Isolated Dog Heart." Japanese Journal of Pharmacology 65, no. 3 (1994): 215–22. http://dx.doi.org/10.1254/jjp.65.215.

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33

Panicucci, Chiara, Lizzia Raffaghello, Santina Bruzzone, et al. "eATP/P2X7R Axis: An Orchestrated Pathway Triggering Inflammasome Activation in Muscle Diseases." International Journal of Molecular Sciences 21, no. 17 (2020): 5963. http://dx.doi.org/10.3390/ijms21175963.

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In muscle ATP is primarily known for its function as an energy source and as a mediator of the “excitation-transcription” process, which guarantees muscle plasticity in response to environmental stimuli. When quickly released in massive concentrations in the extracellular space as in presence of muscle membrane damage, ATP acts as a damage-associated molecular pattern molecule (DAMP). In experimental murine models of muscular dystrophies characterized by membrane instability, blockade of eATP/P2X7 receptor (R) purinergic signaling delayed the progression of the dystrophic phenotype dampening t
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Sikora, Andrew, Judy Liu, Celia Brosnan, Gary Buell, Iain Chessel, and Barry R. Bloom. "Cutting Edge: Purinergic Signaling Regulates Radical-Mediated Bacterial Killing Mechanisms in Macrophages Through a P2X7-Independent Mechanism." Journal of Immunology 163, no. 2 (1999): 558–61. http://dx.doi.org/10.4049/jimmunol.163.2.558.

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Abstract Signaling by extracellular nucleotides through P2 purinergic receptors affects diverse macrophage functions; however, its role in regulating antimicrobial radicals during bacterial infection has not been investigated. Mycobacterium tuberculosis-infected macrophages released ATP in a dose-dependent manner, which correlated with nitrite accumulation. P2 receptor inhibitors, including oxidized ATP, blocked NO synthase (NOSII) up-regulation and NO production induced by infection with M. tuberculosis or bacille Calmette-Guérin, or treatment with LPS or TNF-α. Oxidized ATP also inhibited o
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Rogers, Richard C., David H. McDougal, Sue Ritter, Emily Qualls-Creekmore, and Gerlinda E. Hermann. "Response of catecholaminergic neurons in the mouse hindbrain to glucoprivic stimuli is astrocyte dependent." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 315, no. 1 (2018): R153—R164. http://dx.doi.org/10.1152/ajpregu.00368.2017.

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Hindbrain catecholaminergic (CA) neurons are required for critical autonomic, endocrine, and behavioral counterregulatory responses (CRRs) to hypoglycemia. Recent studies suggest that CRR initiation depends on hindbrain astrocyte glucose sensors (McDougal DH, Hermann GE, Rogers RC. Front Neurosci 7: 249, 2013; Rogers RC, Ritter S, Hermann GE. Am J Physiol Regul Integr Comp Physiol 310: R1102–R1108, 2016). To test the proposition that hindbrain CA responses to glucoprivation are astrocyte dependent, we utilized transgenic mice in which the calcium reporter construct (GCaMP5) was expressed selec
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Johnson, Christopher D., Andrew M. Coney, and Janice M. Marshall. "Roles of norepinephrine and ATP in sympathetically evoked vasoconstriction in rat tail and hindlimb in vivo." American Journal of Physiology-Heart and Circulatory Physiology 281, no. 6 (2001): H2432—H2440. http://dx.doi.org/10.1152/ajpheart.2001.281.6.h2432.

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In anesthetized rats, we characterized the contributions of norepinephrine (NE) and ATP to changes in tail and hindlimb (femoral) vascular resistances (TVR and FVR, respectively) evoked by three patterns of sympathetic stimulation: 1) couplets (2 impulses at 20 Hz), 2) short trains (20 impulses at 20 Hz), and 3) a natural irregular pattern previously recorded from a sympathetic fiber innervating the rat tail artery. All stimuli evoked greater changes in TVR than FVR. Judging from the effects of the α-adrenoceptor antagonist phentolamine, the purinergic receptor antagonist suramin, or α,β-methy
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Leiva-Salcedo, Elias, Claudio Coddou, Felipe E. Rodríguez, et al. "Lipopolysaccharide Inhibits the Channel Activity of the P2X7 Receptor." Mediators of Inflammation 2011 (2011): 1–12. http://dx.doi.org/10.1155/2011/152625.

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The purinergic P2X7 receptor (P2X7R) plays an important role during the immune response, participating in several events such as cytokine release, apoptosis, and necrosis. The bacterial endotoxin lipopolysaccharide (LPS) is one of the strongest stimuli of the immune response, and it has been shown that P2X7R activation can modulate LPS-induced responses. Moreover, a C-terminal binding site for LPS has been proposed. In order to evaluate if LPS can directly modulate the activity of the P2X7R, we tested several signaling pathways associated with P2X7R activation in HEK293 cells that do not expre
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38

Birder, Lori, and Karl-Erik Andersson. "Urothelial Signaling." Physiological Reviews 93, no. 2 (2013): 653–80. http://dx.doi.org/10.1152/physrev.00030.2012.

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The urothelium, which lines the inner surface of the renal pelvis, the ureters, and the urinary bladder, not only forms a high-resistance barrier to ion, solute and water flux, and pathogens, but also functions as an integral part of a sensory web which receives, amplifies, and transmits information about its external milieu. Urothelial cells have the ability to sense changes in their extracellular environment, and respond to chemical, mechanical and thermal stimuli by releasing various factors such as ATP, nitric oxide, and acetylcholine. They express a variety of receptors and ion channels,
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Lapel, Martin, Philip Weston, Derek Strassheim, et al. "Glycolysis and oxidative phosphorylation are essential for purinergic receptor-mediated angiogenic responses in vasa vasorum endothelial cells." American Journal of Physiology-Cell Physiology 312, no. 1 (2017): C56—C70. http://dx.doi.org/10.1152/ajpcell.00250.2016.

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Angiogenesis is an energy-demanding process; however, the role of cellular energy pathways and their regulation by extracellular stimuli, especially extracellular nucleotides, remain largely unexplored. Using metabolic inhibitors of glycolysis (2-deoxyglucose) and oxidative phosphorylation (OXPHOS) (oligomycin, rotenone, and FCCP), we demonstrate that glycolysis and OXPHOS are both essential for angiogenic responses of vasa vasorum endothelial cell (VVEC). Treatment with P2R agonists, ATP, and 2-methylthioadenosine diphosphate trisodium salt (MeSADP), but not P1 receptor agonist, adenosine, in
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Blasetti Fantauzzi, Claudia, Stefano Menini, Carla Iacobini, et al. "Deficiency of the Purinergic Receptor 2X7 Attenuates Nonalcoholic Steatohepatitis Induced by High-Fat Diet: Possible Role of the NLRP3 Inflammasome." Oxidative Medicine and Cellular Longevity 2017 (2017): 1–14. http://dx.doi.org/10.1155/2017/8962458.

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Molecular mechanisms driving transition from simple steatosis to nonalcoholic steatohepatitis (NASH), a critical step in the progression of nonalcoholic fatty liver disease (NAFLD) to cirrhosis, are poorly defined. This study aimed at investigating the role of the purinergic receptor 2X7 (PR2X7), through the NLRP3 inflammasome, in the development of NASH. To this end, mice knockout for the Pr2x7 gene (Pr2x7−/−) and coeval wild-type (WT) mice were fed a high-fat diet (HFD) or normal-fat diet for 16 weeks. NAFLD grade and stage were lower in Pr2x7−/− than WT mice, and only 1/7 Pr2x7−/− animals s
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Homolya, László, Thomas H. Steinberg, and Richard C. Boucher. "Cell to Cell Communication in Response to Mechanical Stress via Bilateral Release of Atp and Utp in Polarized Epithelia." Journal of Cell Biology 150, no. 6 (2000): 1349–60. http://dx.doi.org/10.1083/jcb.150.6.1349.

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Airway epithelia are positioned at the interface between the body and the environment, and generate complex signaling responses to inhaled toxins and other stresses. Luminal mechanical stimulation of airway epithelial cells produces a propagating wave of elevated intracellular Ca2+ that coordinates components of the integrated epithelial stress response. In polarized airway epithelia, this response has been attributed to IP3 permeation through gap junctions. Using a combination of approaches, including enzymes that destroy extracellular nucleotides, purinergic receptor desensitization, and air
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MIMIKAKIS, L. John, L. David NELSON, and R. Robin PRESTON. "Oscillating response to a purine nucleotide disrupted by mutation in Paramecium tetraurelia." Biochemical Journal 330, no. 1 (1998): 139–47. http://dx.doi.org/10.1042/bj3300139.

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The purine nucleotide GTP, when added extracellularly, induces oscillations in the swimming behaviour of the protist Paramecium tetraurelia. For periods as long as 10 min the cell swims backwards and forwards repetitively. The oscillations in swimming behaviour are driven by changes in membrane potential of the cell, which in turn are caused by periodic activation of inward Mg2+- and Na+-specific currents. We screened for and isolated mutants that are defective in this response, exploiting the fact that the net result of GTP on a population of cells is repulsion. One mutant, GTP-insensitive (g
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Cibelli, Antonio, Preeti Dohare, David C. Spray, and Eliana Scemes. "Differential activation of mouse and human Panx1 channel variants." PLOS ONE 18, no. 12 (2023): e0295710. http://dx.doi.org/10.1371/journal.pone.0295710.

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Pannexins are ubiquitously expressed in human and mouse tissues. Pannexin 1 (Panx1), the most thoroughly characterized member of this family, forms plasmalemmal membrane channels permeable to relatively large molecules, such as ATP. Although human and mouse Panx1 amino acid sequences are conserved in the presently known regulatory sites involved in trafficking and modulation of the channel, differences are reported in the N- and C-termini of the protein, and the mechanisms of channel activation by different stimuli remain controversial. Here we used a neuroblastoma cell line to study the activ
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Salcman, Barbora, Rajia Bahri, Peter W. West, Chiara Tontini, Karen Affleck, and Silvia Bulfone-Paus. "P2X7 Receptor-Induced Human Mast Cell Degranulation Is Enhanced by Interleukin 33." International Journal of Molecular Sciences 25, no. 3 (2024): 1730. http://dx.doi.org/10.3390/ijms25031730.

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MCs are tissue-resident immune cells that strategically reside in barrier organs and respond effectively to a wide range of stimuli, such as IL-33, a mediator released upon epithelial damage. Adenosine triphosphate (ATP) accumulates at sites of tissue injury and is known to modulate MC activities. This study investigated how an inflammatory tissue environment rich in IL-33 modulates the ATP-mediated activation of MCs. Human primary MCs primed with IL-33 displayed a strongly increased response to ATP but not ADP. This resulted in increased degranulation, IL-8 release, and pERK1/2 signalling. Su
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Hanidziar, Dusan, and Simon C. Robson. "Synapomorphic features of hepatic and pulmonary vasculatures include comparable purinergic signaling responses in host defense and modulation of inflammation." American Journal of Physiology-Gastrointestinal and Liver Physiology 321, no. 2 (2021): G200—G212. http://dx.doi.org/10.1152/ajpgi.00406.2020.

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Hepatosplanchnic and pulmonary vasculatures constitute synapomorphic, highly comparable networks integrated with the external environment. Given functionality related to obligatory requirements of “feeding and breathing,” these organs are subject to constant environmental challenges entailing infectious risk, antigenic and xenobiotic exposures. Host responses to these stimuli need to be both protective and tightly regulated. These functions are facilitated by dualistic, high-low pressure blood supply of the liver and lungs, as well as tolerogenic characteristics of resident immune cells and si
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Hesse, Julia, Mona K. Rosse, Bodo Steckel, et al. "Mono-ADP-ribosylation sites of human CD73 inhibit its adenosine-generating enzymatic activity." Purinergic Signalling 18, no. 1 (2021): 115–21. http://dx.doi.org/10.1007/s11302-021-09832-4.

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AbstractCD73-derived adenosine plays a major role in damage-induced tissue responses by inhibiting inflammation. Damage-associated stimuli, such as hypoxia and mechanical stress, induce the cellular release of ATP and NAD+ and upregulate the expression of the nucleotide-degrading purinergic ectoenzyme cascade, including adenosine-generating CD73. Extracellular NAD+ also serves as substrate for mono-ADP-ribosylation of cell surface proteins, which in human cells is mediated by ecto-ADP-ribosyltransferase 1 (ARTC1). Here we explored, whether human CD73 enzymatic activity is regulated by mono-ADP
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von Muecke-Heim, Iven-Alex, Clemens Ries, Lidia Urbina, and Jan M. Deussing. "P2X7R antagonists in chronic stress-based depression models: a review." European Archives of Psychiatry and Clinical Neuroscience 271, no. 7 (2021): 1343–58. http://dx.doi.org/10.1007/s00406-021-01306-3.

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AbstractDepression affects around 320 million people worldwide. Growing evidence proposes the immune system to be the core interface between psychosocial stress and the neurobiological and behavioural features of depression. Many studies have identified purinergic signalling via the P2X7 receptor (P2X7R) to be of great importance in depression genesis yet only a few have evaluated P2X7R antagonists in chronic stress-based depression models. This review summarizes their findings and analyses their methodology. The four available studies used three to nine weeks of unpredictable, chronic mild st
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Jones, Rachel J., David Jourd'heuil, John C. Salerno, Susan M. E. Smith, and Harold A. Singer. "iNOS regulation by calcium/calmodulin-dependent protein kinase II in vascular smooth muscle." American Journal of Physiology-Heart and Circulatory Physiology 292, no. 6 (2007): H2634—H2642. http://dx.doi.org/10.1152/ajpheart.01247.2006.

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Nitric oxide synthase (NOS) expression is regulated transcriptionally in response to cytokine induction and posttranslationally by palmitoylation and trafficking into perinuclear aggresome-like structures. We investigated the effects of multifunctional calcium/calmodulin-dependent protein kinase II protein kinase (CaMKII) on inducible NOS (iNOS) trafficking in cultured rat aortic vascular smooth muscle cells (VSMCs). Immunofluorescence and confocal microscopy demonstrated colocalization of iNOS and CaMKIIδ2 with a perinuclear distribution and concentration in aggresome-like structures identifi
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Zohar, Keren, Elyad Lezmi, Fanny Reichert, et al. "Coordinated Transcriptional Waves Define the Inflammatory Response of Primary Microglial Culture." International Journal of Molecular Sciences 24, no. 13 (2023): 10928. http://dx.doi.org/10.3390/ijms241310928.

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The primary role of microglia is to maintain homeostasis by effectively responding to various disturbances. Activation of transcriptional programs determines the microglia’s response to external stimuli. In this study, we stimulated murine neonatal microglial cells with benzoyl ATP (bzATP) and lipopolysaccharide (LPS), and monitored their ability to release pro-inflammatory cytokines. When cells are exposed to bzATP, a purinergic receptor agonist, a short-lived wave of transcriptional changes, occurs. However, only combining bzATP and LPS led to a sustainable and robust response. The transcrip
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Mackey, Cole, Yuning Feng, Chenyu Liang, et al. "Mechanical Modulation, Physiological Roles, and Imaging Innovations of Intercellular Calcium Waves in Living Systems." Cancers 17, no. 11 (2025): 1851. https://doi.org/10.3390/cancers17111851.

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Long-range intercellular communication is essential for multicellular biological systems to regulate multiscale cell–cell interactions and maintain life. Growing evidence suggests that intercellular calcium waves (ICWs) act as a class of long-range signals that influence a broad spectrum of cellular functions and behaviors. Importantly, mechanical signals, ranging from single-molecule-scale to tissue-scale in vivo, can initiate and modulate ICWs in addition to relatively well-appreciated biochemical and bioelectrical signals. Despite these recent conceptual and experimental advances, the full
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