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 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-alpha-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-HT1 receptor acting through calcium and a 5-HT2 receptor which mediates its effects through cyclic AMP.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000096:biosynthesis*; D004175:Diptera; D004305:Dose-Response Relationship, Drug; D007294:Inositol / Q000378:metabolism; D011985:Receptors, Serotonin / Q000032:analysis* / Q000502:physiology; D012469:Salivary Glands / Q000032:analysis* / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; D007294:Inositol; D000242:Cyclic AMP; D002118:Calcium