| Our laboratory has long been interested in identifying new regulators of mammalian salivary gland function, particularly the rat submandibular gland (SMG). It was reported previously by our research group, that in the isolated perfused rat SMG, 5-HT decreases acetylcholine-induced salivary flow and markedly increases saliva protein content (J Dent Res 75:935). These functional effects were accompanied by an increase in cyclic AMP production in dispersed cell aggregates from the rat SMG in response to 5-HT, suggesting that 5-HT receptors positively coupled to adenylyl cyclase are expressed in this organ. The first aim of this dissertation project was to identify the 5-HT receptor subtypes that mediate these effects in rat SMG. Data from these studies utilizing both pharmacological and molecular techniques, indicated the presence of mRNA for 5-HT4(b) and 5-HT7(a), but not for 5-HT4(a), 5-ht6 and 5-HT7(b,c) ( Brit J Pharmacol 130:104). The second aim has been to localize 5-HT 4(b) and 5-HT7(a) receptor expression among the major cells types in the rat SMG and to assess changes in 5-HT receptor expression during development. Our findings to date, including results from studies in progress, suggest that the 5-HT4(b) receptor is primarily expressed in duct cells, whereas, the 5-HT7(a) receptor appears to be mainly associated with the acini. Additionally, preliminary data strongly suggest that 5-HT receptor expression in the rat SMG is developmentally regulated. 5-HT stimulation of cyclic AMP production in SMG is very low in newborn animals and increases dramatically as a function of animal age during the developmentally critical first 4–6 weeks following birth.; The list of agents shown to be involved in the regulation of salivary gland function has increased steadily in recent years. The identification of two AC-coupled 5-HT receptor subtypes in rat SMG suggests that this list may eventually include 5-HT. Knowledge of discrete 5-HT receptor splice variant expression patterns in the rat SMG broadens the scope of what is thought to be the role of this genetic variation among 5-HT receptors, and how they may regulate salivary gland physiology. |
