Electrophysiological evidence for the existence of separate receptor mechanisms mediating the action of 5-hydroxytryptamine.

The transepithelial potential recorded across the salivary gland of the blowfly Calliphora responded to 5-hydroxytryptamine (5-HT) with a complex depolarising response characterised by oscillatory activity at low doses. A rapid screening procedure for characterizing the electrophysiological response of the gland to 5-HT and its analogues was developed. It consisted of recording the potential during the gradual addition of the agent in the form of a ramp. 5-HT gave a characteristic electrophysiological signature which was then compared with that of other analogues. Tryptamine, bufotenine and dimethyltryptamine gave potential signatures very similar to those of 5-HT. Histamine, 4- and 5-fluoro-alpha-methyltryptamine gave s predominantly hyperpolarising response which is characteristic of the effect produced by cyclic AMP. Analogues with substituents at the 5-position (methyl, methoxy, chloro) and 4-hydroxytryptamine gave a depolarising response indicative of a predominantly calcium effect. It is concluded that 5-HT acts through separate transducing mechanisms. The depolarizing response seems to indicate an action through calcium whereas the hyperpolarizing response might be mediated through cyclic AMP. Whether or not these separate responses are linked to different 5-HT receptors remains to be determined.