1. 5-HT4 receptor mediated stimulation of gastric emptying in rats.
- Author
-
Hegde SS, Wong AG, Perry MR, Ku P, Moy TM, Loeb M, and Eglen RM
- Subjects
- Analysis of Variance, Animals, Benzamides pharmacology, Drug Interactions, Male, Pyrroles pharmacology, Rats, Rats, Sprague-Dawley, Receptors, Serotonin, 5-HT4, Serotonin Receptor Agonists pharmacology, Gastric Emptying physiology, Receptors, Serotonin physiology
- Abstract
It is well documented that certain substituted benzamides, such as cisapride, and benzimidazolones, such as BIMU 8, enhance gastric emptying in rats. As these compounds possess 5-HT3 antagonistic and 5-HT4 agonistic properties, the precise mechanisms (5-HT3 or 5-HT4) underlying their gastroprokinetic effects is still unclear. In the present study, we used SC 49518 (a benzamide and selective 5-HT4 receptor agonist) and two selective 5-HT4 receptor antagonists (RS 23597-190 and SB 204070) to elucidate the role of 5-HT4 receptors in gastroprokinesis. SC 49518 (1-316 micrograms/kg; ip) produced significant and dose-dependent stimulation of gastric emptying in rats (ED50 = 2.3 micrograms/kg; ip). SC 49518 also produced dose-dependent inhibition of bradycardia induced by 2-methyl 5-HT (von Bezold-Jarisch reflex) but with a 156 fold lower potency (ID50 = 0.36 mg/kg; ip). The gastroprokinetic effects of SC 49518 (3-316 micrograms/kg; ip) were significantly antagonized by the selective 5-HT4 receptor antagonist RS 23597-190 (0.1 mg/kg/min; iv). SB 204070 (0.003-1 mg/kg; ip), another selective 5-HT4 receptor antagonist, produced dose-dependent inhibition of the gastroprokinetic effects of SC 49518 (10 micrograms/kg; ip), the inhibition attaining statistical significance at the dose of 0.1 mg/kg; ip. RS 23597-190 had no effects on gastric emptying per se whereas SB 204070 significantly increased gastric emptying by itself at 1 mg/kg; ip but not at 0.1 mg/kg; ip. These findings show, for the first time, that SC 49518, a selective 5-HT4 receptor agonist, produces potent stimulation of gastric emptying in rats via a mechanism involving activation of 5-HT4 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1995
- Full Text
- View/download PDF