SEPARATE 5‐HYDROXYTRYPTAMINE RECEPTORS ON THE SALIVARY GLAND OF THE BLOWFLY ARE LINKED TO THE GENERATION OF EITHER CYCLIC ADENOSINE 3‘,5’‐MONOPHOSPHATE OR CALCIUM SIGNALS

1 5 ‐Hydroxytryptamine (5 ‐HT) stimulates the formation of two separate second messengers in the salivary gland of the blowfly. Activation of adenylate cyclase raises cyclic adenosine 3′, 5′‐monophosphate (cyclic AMP) whereas the hydrolysis of phosphatidylinositol (PI) is associated with an increase in calcium permeability. The possibility that these two signal pathways might be controlled by separate 5‐HT receptors was studied by testing the specificity of 5‐HT analogues and antagonists. 2 The parent compound 5‐HT was found to stimulate both cyclic AMP formation and the related parameters of PI hydrolysis and calcium transport with similar dose‐response relationships. 3 Certain analogues such as 4‐ and 5‐fluoro‐α‐methyltryptamine were capable of raising cyclic AMP levels and stimulating fluid secretion but did not stimulate the hydrolysis of PI or the entry of calcium. 4 Other analogues, which had chloro or methyl substituents at the 5‐position, were found to stimulate the hydrolysis of PI and the transport of calcium at much lower doses than those required to stimulate the formation of cyclic AMP. 5 Antagonists were also found to exert selective effects. Methysergide was a potent inhibitor of PI hydrolysis whereas cinanserin was far more selective in blocking the stimulatory effect of 5‐HT on cyclic AMP formation. 6 It is concluded that 5‐HT acts on two separate receptors, a 5‐HT 1 receptor acting through calcium and a 5‐HT 2 receptor which mediates its effects through cyclic AMP.