Induction mechanism of oral dryness by the sialogogue pilocarpine

匹罗卡品和西维蜜林可诱导唾液分泌，并在口腔内湿润。我们发现，在大鼠的腹膜腔和脑室内注射毛果芸香碱可引起大鼠的水摄取，而侧脑室预先注射阿托品可抑制这种行为。匹罗卡品可增加穹隆下器、视前区正中核和终板血管器内c-Fos阳性神经元的数量，这些部位可能构成脑内的口渴中枢。匹罗卡品直接影响和去极化脑片制备的穹隆下器官的神经元。另一方面，腹腔注射西维米林并没有增加水摄入量，而是抑制了血管紧张素II诱导的水摄入量。匹罗卡品和西维米林在体外制剂中增加唾液腺腺泡细胞内钙浓度。体外给药引起的细胞内钙离子浓度的升高比体内给药的增加要短。因此，匹罗卡品和西维蜜林通过相同的细胞内第二信使系统对唾液腺的腺泡细胞起作用。这些结果表明，匹罗卡品和Cevimeline在中枢神经系统和外周器官中具有不同的作用。

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.