Differences between receptors for 5-hydroxytryptamine on autonomic neurones revealed by nor-(-)-cocaine

1 The interaction between nor-(-)-cocaine and 5-hydroxytryptamine (5-HT) at autonomic neuronal 5-hydroxytryptamine (5-HT) receptors has been investigated on the rabbit heart and guinea-pig ileum. 2 The chronotropic response to 5-HT mediated through activation of receptors on the terminal sympathetic fibres of the rabbit heart was antagonized selectively and surmountably by nor-(-)-cocaine. Schild analysis yielded a pA2 value for the interaction of 7.79 +/- 0.11, n = 13. 3 On the guinea-pig ileum induced to contract by activation of 5-HT receptors on the intramural cholinergic nerves, nor-(-)-cocaine was also a selective and surmountable antagonist of 5-HT, although the concentrations needed were higher than those shown to be effective on the heart. The pA2 value for the interaction was 6.49 +/- 0.07, n = 16. 4 The differential blocking effect of nor-(-)-cocaine in the two tissues suggests that the receptors for 5-HT on the cholinergic nerves of the ileum and the sympathetic fibres of the heart are different. The data thus lend support to the earlier similar conclusion based on the observation that 5-methoxytryptamine is a potent agonist on the ileum yet inactive on the heart.