Effects of pilocarpine and cevimeline on Ca2+ mobilization in rat parotid acini and ducts.

Previous reports suggested that there is no significant difference in the binding affinity of pilocarpine and cevimeline on muscarinic receptors (1). However, in vivo studies from our laboratory suggested that pilocarpine-induced salivation from the parotid gland is greater than that induced by cevimeline in rats (2, 3). Therefore, in the present study, sialogogue-induced intracellular Ca2+ mobilization was investigated in isolated parotid gland cells in vitro. Pilocarpine and cevimeline increased the intracellular Ca2+ concentration of parotid gland acinar and duct cells over 1 µM in a dose-dependent manner. Pilocarpine-induced responses were higher than cevimeline-induced responses. Ca2+ responses to both agents were completely blocked by 1 µM 4-DAMP, an M3 muscarinic receptor antagonist. In the absence of extracellular Ca2+, both sialogogues induced transient Ca2+ increase in parotid gland acinar cells. These results suggest that the sialogogues stimulate some common routes via the Ca2+ signaling in parotid gland acinar cells. We also report a significant difference of Ca2+ responses in concentration between pilocarpine and cevimeline in parotid gland acinar cells. The different Ca2+ responses between the sialogogues would explain the different saliva volumes from the parotid gland between them that we have observed in previous in vivo studies (2, 3). J. Med. Invest. 56 Suppl.: 375, December, 2009