Muscarinic Receptors and Hydrolysis of Inositol Phospholipids in Rat Cerebral Cortex and Parotid Gland

Abstract

Exposure of rat brain or parotid gland slices to muscarinic receptor agonists stimulates a phospholipase C that degrades inositol phospholipids. When tissue slices were labeled in vitro with [3H]inositol, this response could be monitored by measuring the formation of [3H]inositol phosphates. Accumulation of inositol 1,4-biphosphate in stimulated brain slices suggests that polyphosphonositides are the primary targets for phospholipase C activity. Li+ (10 mM) in the medium completely blocked the hydrolysis of inositol 1-phosphate, partially inhibited inositol 1,4-bisphosphate hydrolysis, but had no effect on the hydrolysis of inositol 1,4,5-trisphosphate by endogenous phosphatases. Muscarinic receptor pharmacology was studied by measuring the accumulation of [3H]inositol 1-phosphate in the presence of 10 mM Li+. In experiments on brain slices, the response to carbachol was antagonized by atropine with an affinity constant of .apprx. 8.79 .+-. 0.12. Dose-response curves to several muscarinic agonists were constructed using brain and parotid gland slices. Full agonists were relatively more potent in the parotid gland than in the brain. Explanations for these differences are suggested.