Pharmacology of 5-hydroxytryptamine receptors in frog skin epithelium.

1. 5-Hydroxytryptamine (5-HT) stimulates active sodium transport and decreases the passive mucosal to serosal chloride permeability across frog skin. The relative importance of the different regions of the 5-HT molecule in the mediation of these responses has been studied using a range of structurally related compounds. 2. Substitution in the ethyl amine side chain of 5-HT (5-hydroxytryptophan) results in decreased receptor affinity and intrinsic activity; removal of the side chain (5-hydroxyindole) abolishes activity. Methoxy substitution of the 5-OH moiety of 5-HT has no effect on intrinsic activity but reduces affinity; displacement of the hydroxyl group to position 6 diminishes intrinsic activity and affinity. 3. It is concluded that both of the 5-HT-induced physiological effects are mediated via a single receptor which is distinct from alpha- and beta-adrenoceptors.