Purinergic and nitrergic neuromuscular transmission mediates spontaneous neuronal activity in the rat colon

Víctor Gil, Diana Gallego, Laura Grasa, María Teresa Martín, Marcel Jiménez

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46 Citations (Scopus)

Abstract

Nitric oxide (NO) and ATP mediate smooth muscle relaxation in the gastrointestinal tract. However, the involvement of these neurotransmitters in spontaneous neuronal activity is unknown. The aim of the present work was to study spontaneous neuromuscular transmission in the rat midcolon. Microelectrode experiments were performed under constant stretch both in circular and longitudinal directions. Spontaneous inhibitory junction potentials (sIJP) were recorded. Tetrodotoxin (1 μM) and apamin (1 μM) depolarized smooth muscle cells and inhibited sIJP. Nω-nitro-L-arginine (L-NNA, 1 mM) depolarized smooth muscle cells but did not modify sIJP. In contrast, the P2Y1 antagonist MRS-2500 (1 μM) did not modify the resting membrane potential (RMP) but reduced sIJP (IC50 = 3.1 nM). Hexamethonium (200 μM), NF-023 (10 μM), and ondansetron (1 μM) did not modify RMP and sIJP. These results correlate with in vitro (muscle bath) and in vivo (strain gauges) data where L-NNA but not MRS-2500 induced a sustained increase of spontaneous motility. We concluded that, in the rat colon, inhibitory neurons regulate smooth muscle RMP and cause sIJP. In vitro, the release of inhibitory neurotransmitters is independent of nicotinic, P2X, and 5-hydroxytryptamine type 3 receptors. Neuronal NO causes a sustained smooth muscle hyperpolarization that is responsible for a constant inhibition of spontaneous motility. In contrast, ATP acting on P2Y1 receptors is responsible for sIJP but does not mediate inhibitory neural tone. ATP and NO have complementary physiological functions in the regulation of gastrointestinal motility. Copyright © 2010 the American Physiological Society.
Original languageEnglish
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume299
DOIs
Publication statusPublished - 1 Jul 2010

Keywords

  • Gastrointestinal
  • Nitric oxide
  • P2Y receptors 1
  • Spontaneous inhibitory junction potential

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