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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 μm) 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 μm) had a quantitatively similar action to ketanserin (0.1 μm) 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.