Chlorpromazine inhibition of muscarinic-cholinergic responses in the rat parotid gland.

The ability of chlorpromazine (CPZ) to inhibit muscarinic-cholinergic secretory events was studied in vitro in rat parotid acinar cells. CPZ inhibited carbachol-induced amylase release in a dose-dependent fashion but had no effect on that elicited by isoproterenol. The inhibition of parotid protein synthesis induced by carbachol, but not that induced by A23187, was blocked by CPZ. CPZ exhibited a dose-dependent inhibition of [3H] quinuclidinyl benzilate (QNB) binding to muscarinic receptors, and altered the KD of the receptor for the ligand. These results are consistent with an ability of CPZ to inhibit muscarinic-cholinergic-induced salivary secretion by complex interference with receptor binding. In addition, CPZ may block parotid-muscarinic responses by impeding a post-receptor signaling step which is proximal to Ca2+ mobilization.