A REGULATORY ROLE IN MAMMALIAN SALIVARY-GLANDS FOR 5-HYDROXYTRYPTAMINE RECEPTORS COUPLED TO INCREASED CYCLIC-AMP PRODUCTION

Although a functional role for serotonin (5-hydroxytryptamine, 5-HT) h as been defined in the salivary glands of some lower species, relative ly few data supporting a role for 5-HT in the regulation of mammalian salivary glands have been presented. Our initial results from polymera se chain reaction studies in cells of mammalian submandibular gland or igin using consensus sequence primers from G protein-coupled receptors suggested the presence of mRNA for a 5-HT receptor in these cells. Ba sed on this observation, the question of a role for 5-HT in mammalian submandibular gland function was re-addressed, using isolated, perfuse d rat submandibular glands and dispersed-cell aggregates from this gla nd. In perfused glands, 5-HT decreased the rate of saliva flow initiat ed by acetylcholine by about 50% and increased the amount of protein i n the saliva two-fold. In dispersed-cell aggregates, 5-HT elicited a c oncentration-dependent increase in the accumulation of adenosine 3',5' monophosphate (cyclic AMP; EC(50) = 660 +/- 110 nM). In addition, fun ctional studies, as well as radioligand binding experiments, indicated that the effects of 5-HT are independent of beta-adrenoceptors. Accum ulation of cAMP in gland cells was consistent with a direct action of 5-HT on adenylyl cyclase. Similar cyclic AMP responses to 5-HT were ob served in cells isolated from mouse and opossum submandibular glands a nd rat sublingual and parotid glands. Our findings suggest the presenc e of a 5-HT receptor in mammalian salivary glands coupled to the stimu lation of adenylyl cyclase and, at least in rat submandibular gland, i nvolved in modifying the volume and protein content of saliva.