STIMULANT EFFECTS OF 5-HYDROXYTRYPTAMINE ON GUINEA-PIG STOMACH PREPARATIONS IN-VITRO

5-Hydroxytryptamine (5-HT) contracts and relaxes isolated stomach prep arations. This study attempts to characterise receptors involved in th e contractile response using electrically stimulated circular muscle s trips from guinea pig stomach. Electrically induced contractions were abolished by atropine and tetrodotoxin. 5-HT enhanced contractions in corpus and fundus strips with pEC(50%) values (-log(10) of the concent rations causing a 50% increase in twitch height) of 9.6 and 9.1, respe ctively. 5-Carboxamidotryptamine and 8-OH-DPAT (8-hydroxy-2-(di-n-prop ylamino)tetralin) 5-HT1A receptor agonists, and alpha-methyl-5-HT, an agonist at 5-HT2 receptors, reduced contractions. The 5-HT3 receptor a gonist, 2-methyl-5-HT, increased contractions. The effect of 2-methyl- 5-HT but not of 5-HT was antagonized by the 5-HT3 receptor antagonist, tropisetron (10(-7) M). The 5-HT3 receptor antagonists, tropisetron, MDL 72222 (1 alpha H,3 alpha,5 alpha H-tropan-3-yl-3,5-dichlorobenzoat e), granisetron and ondansetron, did not modify twitch responses at co ncentrations below 10(-7) M. Renzapride and metoclopramide, agonists a t 5-HT4 receptors, increased contractions and this effect was inhibite d by the 5-HT4 receptor antagonist SDZ 205-557 (2-methoxy-4-amino-5-ch loro-benzoic acid 2-(diethylamino) ethyl ester) with a pA(2) of 7.4. T he effect of 5-HT at a submaximal concentration of 10(-8) M was blocke d by SDZ 205-557 (10(-6) M). It is concluded that electrically induced contractions in guinea pig stomach strips are enhanced by activation of 5-HT3- and 5-HT4 receptors and are diminished by 5-HT1 receptor ago nists. Stimulant physiological responses to 5-HT are probably mediated via 5-HT4 receptors unless very high concentrations of 5-HT are relea sed.