EVIDENCE THAT THE 5-HT3 RECEPTORS OF THE RAT, MOUSE AND GUINEA-PIG SUPERIOR CERVICAL-GANGLION MAY BE DIFFERENT

1 Using grease-gap recordings from the isolated superior cervical ganglion of mouse, rat and guinea-pig, we have compared the depolarization evoked by 5-hydroxytryptamine (5-HT) with that evoked by the selective 5-HT3 receptor agonist 2-methyl-5-HT (2-Me-5-HT). 2 The maximum depolarization induced by 2-Me-5-HT was smaller than that induced by 5-HT in all three species, and particularly in the guinea-pig. 3 The 5-HT2 receptor antagonist ketanserin (1-mu-M) caused a clear rightward shift of the dose-response curve to 5-HT on the guinea-pig ganglion, but not on the mouse or rat ganglion. Spiperone (0.03-mu-M) had a quantitatively similar action to ketanserin (0.1-mu-M) on the 5-HT dose-response curve of the guinea-pig ganglion. Ketanserin had no significant effect on the dose-response curve to 2-Me-5-HT on any of these ganglia. 4 Using 2-Me-5-HT as the agonist, we determined the pA2 values for two 5-HT3 receptor antagonists. The potency of ICS 205-930 varied by approximately 100 fold between the species and that of (+)-tubocurarine varied by over 1000 fold. The differences in the pA2 values of these compounds varied independently among the species. 5 We conclude that 5-HT3 receptors are present on the superior cervical ganglion from the rat, mouse and guinea-pig, but these receptors may be pharmacologically distinct from each other. In addition, the depolarization of the guinea-pig superior cervical ganglion by low concentrations of 5-HT is largely mediated by ketanserin-sensitive receptors.