QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.103.053512v1 307/2/460    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Grider, J. R. Search for Related Content PubMed PubMed Citation Articles by Grider, J. R.

GASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Neurotransmitters Mediating the Intestinal Peristaltic Reflex in the Mouse

Departments of Physiology and Medicine, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia

The motor, modulatory, and sensory neurotransmitters that mediate the peristaltic reflex in the mouse colon were identified by direct measurement, and their involvement in various pathways was determined by selective receptor antagonists. Mucosal stimulation in the central compartment of a three-compartment flat sheet preparation of mouse colon elicited ascending contraction and descending relaxation in the orad and caudad compartments, respectively. Ascending contraction was accompanied by substance P release, a marker for excitatory neurotransmitter release, into the orad compartment and was partly inhibited by atropine and spantide, and abolished by a combination of the two antagonists. Descending relaxation was accompanied by vasoactive intestinal peptide (VIP) release, a marker for inhibitory neurotransmitter release, into the caudad compartment, and was partly inhibited by VIP_10-28 and N^G-nitro-L-arginine, and abolished by a combination of the two agents. Somatostatin release increased during descending relaxation: immunoneutralization of somatostatin or blockade of its effect with a selective somatostatin type 2 receptor antagonist inhibited descending relaxation. The -opioid receptor antagonist naltrindole augmented descending relaxation and ascending contraction. Calcitonin gene-related peptide (CGRP) release increased in the central compartment and was mediated by concurrent release of 5-hydroxytryptamine (5-HT) because its release was blocked by a 5-HT₄ receptor antagonist. Both the latter and the CGRP antagonist CGRP_8-37, inhibited ascending contraction and descending relaxation. Thus, the reflex in mouse like that in rat and human intestine is initiated by mucosal release of 5-HT and activation of 5-HT₄ receptors on CGRP sensory neurons and is relayed via somatostatin and opioid interneurons to VIP/nitric-oxide synthase inhibitory motor neurons and via cholinergic interneurons to acetylcholine/tachykinin excitatory motor neurons.

Address correspondence to: Dr. J. R. Grider, Department of Physiology, P.O. Box 980551, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298. E-mail: jgrider{at}hsc.vcu.edu

This article has been cited by other articles:

				M. A. F. de Godoy, N. Rattan, and S. Rattan Arachidonic acid metabolites follow the preferential course of cyclooxygenase pathway for the basal tone in the internal anal sphincter Am J Physiol Gastrointest Liver Physiol, April 1, 2009; 296(4): G727 - G734. [Abstract] [Full Text] [PDF]

				K. Tsukamoto, H. Ariga, C. Mantyh, T. N. Pappas, H. Yanagi, T. Yamamura, and T. Takahashi Luminally released serotonin stimulates colonic motility and accelerates colonic transit in rats Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2007; 293(1): R64 - R69. [Abstract] [Full Text] [PDF]

				S. K. Sarna Enteric descending and afferent neural signaling stimulated by giant migrating contractions: essential contributing factors to visceral pain Am J Physiol Gastrointest Liver Physiol, February 1, 2007; 292(2): G572 - G581. [Abstract] [Full Text] [PDF]

				L. Wang, V. Martinez, H. Kimura, and Y. Tache 5-Hydroxytryptophan activates colonic myenteric neurons and propulsive motor function through 5-HT4 receptors in conscious mice Am J Physiol Gastrointest Liver Physiol, January 1, 2007; 292(1): G419 - G428. [Abstract] [Full Text] [PDF]

				W. Cao, K. M. Harnett, and V. E. Pricolo NK2 Receptor-Mediated Spontaneous Phasic Contractions in Normal and Ulcerative Colitis Human Sigmoid Colon J. Pharmacol. Exp. Ther., June 1, 2006; 317(3): 1349 - 1355. [Abstract] [Full Text] [PDF]

				M. Liu, M. S. Geddis, Y. Wen, W. Setlik, and M. D. Gershon Expression and function of 5-HT4 receptors in the mouse enteric nervous system Am J Physiol Gastrointest Liver Physiol, December 1, 2005; 289(6): G1148 - G1163. [Abstract] [Full Text] [PDF]

				D. Patton, M. O'Reilly, and S. Vanner Sensory peptide neurotransmitters mediating mucosal and distension evoked neural vasodilator reflexes in guinea pig ileum Am J Physiol Gastrointest Liver Physiol, November 1, 2005; 289(5): G785 - G790. [Abstract] [Full Text] [PDF]