Mechanisms Underlying Hyperpolarization Evoked by P2y Receptor Activation in Mouse Distal Colon.
From: Dipartimento di Biologia Cellulare e dello Sviluppo — Laboratorio di Fisiologia generale — Università di Palermo — Viale delle Scienze, 90128 Palermo, Italy.
European journal of pharmacology
- Publish Date: Aug 2006
- ISSN: 0014-2999
- Volume: 544
- Issue: 1-3
- Pages: 174-80
- Medium: Print
- Language: English
- Citation (JAMA): Zizzo Maria Grazia, Mulè Flavia, Serio Rosa, et al. Mechanisms Underlying Hyperpolarization Evoked by P2y Receptor Activation in Mouse Distal Colon.. Eur. J. Pharmacol. Aug 2006;544:174-80
Abstract
In murine colonic circular muscle, ATP mediates fast component of the nerve-evoked inhibitory junction potentials, via activation of P2Y receptors and opening of apamin-sensitive Ca2+-dependent K+ channels. We investigated, using microelectrode recordings, the intracellular events following P2Y-receptor activation by electrical field stimulation or by adenosine 5’-O-2-thiodiphosphate (ADPbetaS), ATP stable analogue. The fast-inhibitory junction potential amplitude was reduced by thapsigargin or ciclopiazonic acid (CPA), sarcoplasmic reticulum Ca2+-ATPase inhibitors, by ryanodine, which inhibits Ca2+ release from ryanodine-sensitive stores, and by 9-(tetrahydro-2-furanyl)-9H-purin-6-amine (SQ 22,536), an adenylyl cyclase inhibitor. Fast-inhibitory junction potentials were enhanced by 2-aminoethoxy-diphenylborate (2-APB), an IP3 receptor inhibitor or by {1-[6((17beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl]-1H-pyrrole-2,5-dione} (U-73122), a phospholipase C inhibitor. ADPbetaS induced hyperpolarization that was significantly reduced by apamin, thapsigargin, CPA, ryanodine, 2-APB and SQ 22,536, but it was not modified by U-73122. Forskolin, an adenylyl cyclase activator, induced hyperpolarization that was inhibited by SQ 22,536, apamin or ryanodine. In conclusion, in murine colon, apamin-sensitive hyperpolarization induced by activation of P2Y receptors is mainly mediated by release of Ca2+ from intracellular ryanodine-dependent stores via a mechanism involving adenylyl cyclase.
Mesh Headings (Keywords): Adenylate Cyclase, Animals, Calcium, Colon, Dose-Response Relationship, Drug, Electrophysiology, Forskolin, Male, Mice, Mice, Inbred C57BL, Models, Statistical, Neurons, Potassium Channels, Calcium-Activated, Receptors, Adrenergic, alpha-1, Receptors, Purinergic P2
Check for Full Text / PubMed Unique Identifier (PMID): 16843454
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