P2Y receptors mediate Ca2+signaling in duodenocytes and contribute to duodenal mucosal bicarbonate secretion
| Autor: | Jimmy Y. C. Chow, Eric J. Smoll, Xiao Dong, Paul A. Insel, Jonathan Lee, Hui Dong, Kwang Hyun Ko, Hong Dong Kim |
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| Rok vydání: | 2009 |
| Předmět: |
P2Y receptor
Time Factors Physiology Uridine Triphosphate Membrane Potentials Receptors Purinergic P2Y2 Mice chemistry.chemical_compound Purinergic P2 Receptor Antagonists Estrenes Intestinal Mucosa Receptor Mice Knockout Purinergic receptor Gastroenterology Hydrogen-Ion Concentration Calcium Channel Blockers Pyrrolidinones Adenosine Diphosphate Pyridoxal Phosphate Aminoquinolines Female medicine.drug Boron Compounds medicine.medical_specialty Nifedipine Duodenum Suramin Biology Cell Line Dogs Mucosal Biology Physiology (medical) Internal medicine medicine Extracellular Animals PPADS Channel blocker Calcium Signaling Intestinal Secretions Hepatology Receptors Purinergic P2 Epithelial Cells Mice Inbred C57BL Bicarbonates Adenosine diphosphate Endocrinology chemistry |
| Zdroj: | American Journal of Physiology-Gastrointestinal and Liver Physiology. 296:G424-G432 |
| ISSN: | 1522-1547 0193-1857 |
| DOI: | 10.1152/ajpgi.90314.2008 |
| Popis: | Since little is known about the role of P2Y receptors (purinoceptors) in duodenal mucosal bicarbonate secretion (DMBS), we sought to investigate the expression and function of these receptors in duodenal epithelium. Expression of P2Y2receptors was detected by RT-PCR in mouse duodenal epithelium and SCBN cells, a duodenal epithelial cell line. UTP, a P2Y2-receptor agonist, but not ADP (10 μM), significantly induced murine duodenal short-circuit current and DMBS in vitro; these responses were abolished by suramin (300 μM), a P2Y-receptor antagonist, or 2-aminoethoxydiphenyl borate (2-APB; 100 μM), a store-operated channel blocker. Mucosal or serosal addition of UTP induced a comparable DMBS in wild-type mice, but markedly impaired response occurred in P2Y2knockout mice. Acid-stimulated DMBS in vivo was significantly inhibited by suramin (1 mM) or PPADS (30 μM). Both ATP and UTP, but not ADP (1 μM), raised cytoplasmic-free Ca2+concentrations ([Ca2+]cyt) with similar potencies in SCBN cells. ATP-induced [Ca2+]cytwas attenuated by U-73122 (10 μM), La3+(30 μM), or 2-APB (10 μM), but was not significantly affected by nifedipine (10 μM). UTP (1 μM) induced a [Ca2+]cyttransient in Ca2+-free solutions, and restoration of external Ca2+(2 mM) raised [Ca2+]cytdue to capacitative Ca2+entry. La3+(30 μM), SK&F96365 (30 μM), and 2-APB (10 μM) inhibited UTP-induced Ca2+entry by 92, 87, and 94%, respectively. Taken together, our results imply that activation of P2Y2receptors enhances DMBS via elevation of [Ca2+]cytthat likely results from an initial increase in intracellular Ca2+release followed by extracellular Ca2+entry via store-operated channel. |
| Databáze: | OpenAIRE |
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