Inhibitory Effect of 5-Hydroxytryptamine on Rat Stomach Fundus: Mediated Indirectly by Activation of Noradrenaline Release

Abstract

Abstract Biphasic cumulative concentration-response curves to 5-hydroxytryptamine (5-HT) and α-methyl-5-hydroxytryptamine (α-Me-5-HT) using rat stomach fundus in the presence of 50 μm pargyline suggested two sites of interaction (high and low affinity). The order of agonist potencies of 5-HT agonists for the high-affinity (contractile) response confirmed reports of a strong correlation of the 5-HT2B (contractile) receptor on fundus with reported rat brain (radioligand binding) pKd values at the 5-HT2C receptor (r = 0·94, b = 0·93 P < 0·01). 1(1-Naphthyl)-piperazine and ketanserin antagonized the high-affinity responses. The order of potencies for the low affinity (inhibitory) response was: α-Me-5-HT > 5-HT. Preincubation with mianserin or S-(—)propranolol, pretreatment with reserpine and removal of the mucosa layer resulted in amplification of the contractile effects and disappearance or reversal of the inhibitory effects of 5-HT. Activation of a second receptor site inducing catecholamine release may explain this effect of 5-HT on rat stomach fundus.