Chlorpromazine Inhibition of Muscarinic-Cholinergic Responses in the Rat Parotid Gland

Abstract

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.

Altered Responses to Agonists after Chronic In Vivo Atropine Administration in Rat Parotid Acini

“…Effect of Chronic Atropine Treatment on Agonist-Induced Ca2+ Mobilization and IP Turnover. Several classes of drugs produce salivary gland hypofunction by interfering with stimulus-secretion coupling of the muscarinic receptor (Batra and Biorklund, 1986;Clemmensen, 1988;Dissing et al, 1990;Unden et al, 1989; Van der Ven et al, 1986).…”

“…Many commonly prescribed medications such as antidepressant and antipsychotic drugs have potent antimuscarinic properties (Batra and Biorklund, 1986;Clemmensen, 1988;Dissing et al, 1990;Unden et al, 1989; Van der Ven et al, 1986). The oral complications of reduced salivary flow are well documented (see Melvin, 1991), for example, an increased susceptibility to dental decay, bacterial and fungal infections, and mucositis.…”