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A Regulatory Role in Mammalian Salivary Glands for 5-Hydroxytryptamine Receptors Coupled to Increased Cyclic AMP Production

Department of Pharmacology, M561 Health Sciences Center, University of Missouri-Columbia, Columbia, Missouri 65212, USA

D.M. Sullivan

National Eye Institute, Building 10 Room 10B17, 9000 Rockville Pike, Bethesda, Maryland 20892

I. Rovira

J.M. Camden

Although a functional role for serotonin (5-hydroxytryptamine, 5-HT) has been defined in the salivary glands of some lower species, relatively few data supporting a role for 5-HT in the regulation of mammalian salivary glands have been presented. Our initial results from polymerase chain reaction studies in cells of mammalian submandibular gland origin using consensus sequence primers from G protein-coupled receptors suggested the presence of mRNA for a 5-HT receptor in these cells. Based on this observation, the question of a role for 5-HT in mammalian submandibular gland function was re-addressed, using isolated, perfused rat submandibular glands and dispersed-cell aggregates from this gland. In perfused glands, 5-HT decreased the rate of saliva flow initiated by acetylcholine by about 50% and increased the amount of protein in the saliva two-fold. In dispersed-cell aggregates, 5-HT elicited a concentration-dependent increase in the accumulation of adenosine 3',5' monophosphate (cyclic AMP; EC₅₀ = 660 ± 110 nM). In addition, functional studies, as well as radioligand binding experiments, indicated that the effects of 5-HT are independent of beta-adrenoceptors. Accumulation 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 observed in cells isolated from mouse and opossum submandibular glands and rat sublingual and parotid glands. Our findings suggest the presence of a 5-HT receptor in mammalian salivary glands coupled to the stimulation of adenylyl cyclase and, at least in rat submandibular gland, involved in modifying the volume and protein content of saliva.

Key Words: 5-hydroxytryptamine receptors • cyclic AMP • salivary secretion

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Journal of Dental Research, Vol. 75, No. 3, 935-941 (1996)
DOI: 10.1177/00220345960750031101


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