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Pharmacological characterization of 5-HT4 receptors mediating relaxation of canine isolated rectum circular smooth muscle.
- Source :
-
British journal of pharmacology [Br J Pharmacol] 1999 Jul; Vol. 127 (6), pp. 1431-7. - Publication Year :
- 1999
-
Abstract
- 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 microM), 5-HT induced relaxation of methacholine (1 microM)-precontracted muscle strips, yielding a monophasic sigmoidal concentration-relaxation curve (pEC50 7.2+/-0.07). Tetrodotoxin (0.3 microM) did not affect the curve to 5-HT, suggesting the inhibitory 5-HT receptor is located on the smooth muscle. Granisetron (0.3 microM) 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 > prucalopride > or = SDZ 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 pK(B) 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 nonhuman species was shown to exhibit relaxant 5-HT4 receptors in the large intestine.
- Subjects :
- 5-Methoxytryptamine pharmacology
Animals
Cisapride pharmacology
Colon drug effects
Colon physiology
Dogs
Dose-Response Relationship, Drug
Female
In Vitro Techniques
Indoles pharmacology
Male
Muscle, Smooth physiology
Receptors, Serotonin physiology
Receptors, Serotonin, 5-HT4
Rectum physiology
Serotonin pharmacology
Serotonin Antagonists pharmacology
Serotonin Receptor Agonists pharmacology
Sulfonamides pharmacology
Muscle Relaxation drug effects
Muscle, Smooth drug effects
Receptors, Serotonin drug effects
Rectum drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0007-1188
- Volume :
- 127
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- British journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 10455293
- Full Text :
- https://doi.org/10.1038/sj.bjp.0702665