JPET xPharm- The Comprehensive Pharmacology Reference

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
 QUICK SEARCH:   [advanced]


     


This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Jin, J.-G.
Right arrow Articles by Grider, J. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jin, J.-G.
Right arrow Articles by Grider, J. R.

Vol. 288, Issue 1, 93-97, January 1999

Propulsion in Guinea Pig Colon Induced by 5-Hydroxytryptamine (HT) via 5-HT4 and 5-HT3 Receptors1

J. -G. Jin, A. E. Foxx-Orenstein and J. R. Grider

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

Previous studies have shown that the intestinal peristaltic reflex initiated by mucosal stimulation is mediated by release of 5-hydroxytryptamine (HT) from enterochromaffin cells; 5-HT acts via 5-HT4 receptors in rat and human, and via both 5-HT4 and 5-HT3 receptors in guinea pig to activate intramural sensory neurons that release calcitonin gene-related peptide. In this study, selective agonists and antagonists were used to examine the involvement of 5-HT4 and 5-HT3 receptors in colonic propulsion. The velocity of propulsion was measured with artificial fecal pellets introduced into the orad end of an isolated guinea pig colonic segment. Control velocity ranged from 0.5 to 3.3 mm/s; mean ± S.E.M., 1.3 ± 0.1 mm/s. The 5-HT4 antagonist, GR 113808A, and the 5-HT3 antagonist, LY 278584, decreased the velocity of pellet propulsion in a concentration-dependent fashion (39 ± 2% and 47 ± 1% decrease at 10 µM, respectively). A combination of both antagonists (10 µM each) was additive, decreasing the velocity by 82 ± 3% to 84 ± 4%. The selective 5-HT4 agonists, HTF 919 and R093877, as well as 5-HT in the presence of the 5-HT2a antagonist, ketanserin, increased the velocity of propulsion in a concentration-dependent fashion with EC50s of 6.9 ± 0.1 nM, 37.4 ± 1.0 nM, and 3.9 ± 0.1 nM, respectively. Compared with HTF 919, R093877 was less potent and appeared to be a partial agonist. All three agonists were effective at submicromolar concentrations; at concentrations above 1 µM, there was no increase in the velocity of propulsion. We conclude that the presence of fecal pellets triggers the release of 5-HT, which acts via both 5-HT3 and 5-HT4 receptors to regulate propulsive activity in guinea pig colon.


0022-3565/99/2881-0093$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 1999 by The American Society for Pharmacology and Experimental Therapeutics



This article has been cited by other articles:


Home page
J. Physiol.Home page
E. J. Dickson, G. W. Hennig, D. J. Heredia, H.-T. Lee, P. O. Bayguinov, N. J. Spencer, and T. K. Smith
Polarized intrinsic neural reflexes in response to colonic elongation
J. Physiol., September 1, 2008; 586(17): 4225 - 4240.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Gastrointest. Liver Physiol.Home page
A. E. Lomax, J. R. O'Hara, N. P. Hyland, G. M. Mawe, and K. A. Sharkey
Persistent alterations to enteric neural signaling in the guinea pig colon following the resolution of colitis
Am J Physiol Gastrointest Liver Physiol, February 1, 2007; 292(2): G482 - G491.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Gastrointest. Liver Physiol.Home page
J. R. Grider and B. E. Piland
The peristaltic reflex induced by short-chain fatty acids is mediated by sequential release of 5-HT and neuronal CGRP but not BDNF
Am J Physiol Gastrointest Liver Physiol, January 1, 2007; 292(1): G429 - G437.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Gastrointest. Liver Physiol.Home page
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]


Home page
Am. J. Physiol. Gastrointest. Liver Physiol.Home page
J. R. Grider
Desensitization of the peristaltic reflex induced by mucosal stimulation with the selective 5-HT4 agonist tegaserod
Am J Physiol Gastrointest Liver Physiol, February 1, 2006; 290(2): G319 - G327.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Gastrointest. Liver Physiol.Home page
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]


Home page
Am. J. Physiol. Gastrointest. Liver Physiol.Home page
Y. Kojima, T. Nakagawa, R. Katsui, H. Fujii, Y. Nakajima, and M. Takaki
A 5-HT4 agonist, mosapride, enhances intrinsic rectorectal and rectoanal reflexes after removal of extrinsic nerves in guinea pigs
Am J Physiol Gastrointest Liver Physiol, August 1, 2005; 289(2): G351 - G360.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Gastrointest. Liver Physiol.Home page
J. R. O'Hara, W. Ho, D. R. Linden, G. M. Mawe, and K. A. Sharkey
Enteroendocrine cells and 5-HT availability are altered in mucosa of guinea pigs with TNBS ileitis
Am J Physiol Gastrointest Liver Physiol, November 1, 2004; 287(5): G998 - G1007.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Gastrointest. Liver Physiol.Home page
X.-C. Bian, L. F. Heffer, R. M. Gwynne, J. C. Bornstein, and P. P. Bertrand
Synaptic transmission in simple motility reflex pathways excited by distension in guinea pig distal colon
Am J Physiol Gastrointest Liver Physiol, November 1, 2004; 287(5): G1017 - G1027.
[Abstract] [Full Text] [PDF]


Home page
J. Neurosci.Home page
T. Sugiuar, K. Bielefeldt, and G. F. Gebhart
TRPV1 Function in Mouse Colon Sensory Neurons Is Enhanced by Metabotropic 5-Hydroxytryptamine Receptor Activation
J. Neurosci., October 27, 2004; 24(43): 9521 - 9530.
[Abstract] [Full Text] [PDF]


Home page
GutHome page
F De Ponti
Pharmacology of serotonin: what a clinician should know
Gut, October 1, 2004; 53(10): 1520 - 1535.
[Full Text] [PDF]


Home page
NEJMHome page
H. R. Mertz
Irritable Bowel Syndrome
N. Engl. J. Med., November 27, 2003; 349(22): 2136 - 2146.
[Full Text] [PDF]


Home page
J. Pharmacol. Exp. Ther.Home page
J. R. Grider
Neurotransmitters Mediating the Intestinal Peristaltic Reflex in the Mouse
J. Pharmacol. Exp. Ther., November 1, 2003; 307(2): 460 - 467.
[Abstract] [Full Text] [PDF]


Home page
J. Pharmacol. Exp. Ther.Home page
T. Tsubouchi, T. Saito, F. Mizutani, T. Yamauchi, and Y. Iwanaga
Stimulatory Action of Itopride Hydrochloride on Colonic Motor Activity in Vitro and in Vivo
J. Pharmacol. Exp. Ther., August 1, 2003; 306(2): 787 - 793.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Gastrointest. Liver Physiol.Home page
H. Shimatani, Y. Kojima, M. Kadowaki, T. Nakagawa, H. Fujii, Y. Nakajima, and M. Takaki
A 5-HT4 agonist mosapride enhances rectorectal and rectoanal reflexes in guinea pigs
Am J Physiol Gastrointest Liver Physiol, July 7, 2003; 285(2): G389 - G395.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
S. Fukumoto, M. Tatewaki, T. Yamada, M. Fujimiya, C. Mantyh, M. Voss, S. Eubanks, M. Harris, T. N. Pappas, and T. Takahashi
Short-chain fatty acids stimulate colonic transit via intraluminal 5-HT release in rats
Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2003; 284(5): R1269 - R1276.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Gastrointest. Liver Physiol.Home page
T. G. Bush, N. J. Spencer, N. Watters, K. M. Sanders, and T. K. Smith
Effects of alosetron on spontaneous migrating motor complexes in murine small and large bowel in vitro
Am J Physiol Gastrointest Liver Physiol, October 1, 2001; 281(4): G974 - G983.
[Abstract] [Full Text] [PDF]


Home page
J. Neurosci.Home page
J. J. Chen, Z. Li, H. Pan, D. L. Murphy, H. Tamir, H. Koepsell, and M. D. Gershon
Maintenance of Serotonin in the Intestinal Mucosa and Ganglia of Mice that Lack the High-Affinity Serotonin Transporter: Abnormal Intestinal Motility and the Expression of Cation Transporters
J. Neurosci., August 15, 2001; 21(16): 6348 - 6361.
[Abstract] [Full Text] [PDF]




Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
 Molecular Interventions Drug Metabolism and Disposition

Copyright © 1999 by the American Society for Pharmacology and Experimental Therapeutics.