Induction mechanism of oral dryness by the sialogogue pilocarpine

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Pilocarpine and cevimeline induce salivary secretion and get wet in the oral cavity. We showed that intraperitoneally and intracerebroventricularly injected pilocarpine elicited water intake in rats and the induced behavior was suppressed by intracerebroventricularly preadministered atropine. The same applications of pilocarpine increased the number of c-Fos positive neurons in the subfornical organ, median nucleus of preoptic area, and organum vasculosum of lamina terminalis, which may constitute the thirst center in the brain. Pilocarpine directly affected and depolarized neurons in the subfornical organ of slice preparations. On the other hand, intraperitoneally injected cevimeline did not increase water intake but rather suppressed angiotensin II-induced water intake. Pilocarpine and cevimeline increased intracellular calcium concentration in acinar cells of the salivary gland in vitro preparations. The increment of intracellular calcium concentration with in vitro application was rather short-lasting than with in vivo application. Thus, pilocarpine and cevimeline show actions on acinar cells of the salivary gland through the same intracellular second messenger system. From these results, it is suggested that pilocarpine and cevimeline have different actions between the central nervous system and the peripheral organs.