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Pharmacological characterization of 5-HT4 receptors mediating relaxation of canine isolated rectum circular smooth muscle
Version of Record online: 29 JAN 2009
1999 Nature Publishing Group
British Journal of Pharmacology
Volume 127, Issue 6, pages 1431–1437, July 1999
How to Cite
Prins, N. H., Van Haselen, J. F. W. R., Lefebvre, R. A., Briejer, M. R., Akkermans, L. M. A. and Schuurkes, J. A. J. (1999), Pharmacological characterization of 5-HT4 receptors mediating relaxation of canine isolated rectum circular smooth muscle. British Journal of Pharmacology, 127: 1431–1437. doi: 10.1038/sj.bjp.0702665
- Issue online: 29 JAN 2009
- Version of Record online: 29 JAN 2009
- (Received January 25, 1999, Revised March 24, 1999, Accepted April 20, 1999)
- 5-HT4 receptors;
- large intestine
This study aimed to characterize for the first time in vitro 5-HT4 receptors in the canine gastrointestinal tract. For this purpose, we used circular muscle strips of the canine isolated rectum.
In the presence of methysergide (60 μM), 5-HT induced relaxation of methacholine (1 μM)-precontracted muscle strips, yielding a monophasic sigmoidal concentration-relaxation curve (pEC50 7.2±0.07).
Tetrodotoxin (0.3 μM) did not affect the curve to 5-HT, suggesting the inhibitory 5-HT receptor is located on the smooth muscle. Granisetron (0.3 μM) did also not affect the curve to 5-HT, which excludes the 5-HT3 receptor mediating the relaxation to 5-HT. The presence of methysergide rules out the involvement of 5-HT1, 5-HT2 or 5-HT7 receptors.
5-HT, the selective 5-HT4 receptor agonists R076186, prucalopride (R093877) and SDZ HTF-919 and the 5-HT4 receptor agonists cisapride and 5-MeOT relaxed the muscle strips with a rank order of potency R076186=5-HT>cisapride>prucaloprideSDZ HTF-919>5-MeOT.
The selective 5-HT4 receptor antagonists GR 125487, RS 39604 and GR 113808 competitively antagonized the relaxations to 5-HT, yielding pKB estimates of 9.7, 7.9 and 9.1, respectively. The selective 5-HT4 receptor antagonist SB 204070 shifted the curve to 5-HT rightward and depressed the maximal response (apparent pA2 10.6). GR 113808 (10 nM) produced a parallel rightward shift of the curve to the selective 5-HT4 receptor agonists R076186 (pA2 8.8).
It is concluded that 5-HT induces relaxation of the canine rectum circular muscle through stimulation of a single population of smooth muscle 5-HT4 receptors. For the first time, a non-human species was shown to exhibit relaxant 5-HT4 receptors in the large intestine.
British Journal of Pharmacology (1999) 127, 1431–1437; doi:10.1038/sj.bjp.0702665