Muscarinic receptors and hydrolysis of inositol phospholipids in rat cerebral cortex and parotid gland.
Exposure of rat brain or parotid gland slices to muscarinic receptor agonists stimulates a phospholipase C that degrades inositol phospholipids. When tissue slices were labelled 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 antagonised by atropine with an affinity constant of approximately 8.79 +/- 0.12. Dose-response curves to several muscarinic agonists were constructed using brain and parotid gland slices. The results are consistent with relatively direct coupling of low-affinity muscarinic receptors to inositol phospholipid breakdown in brain slices; full agonists were relatively more potent in the parotid gland compared with the brain. Explanations for these differences are suggested.
Jacobson
M D
MD
Wusteman
M
M
Downes
C P
CP
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002540:Cerebral Cortex / Q000378:metabolism*; D006868:Hydrolysis; D007295:Inositol Phosphates / Q000378:metabolism; D008094:Lithium / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology; D010306:Parotid Gland / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D011976:Receptors, Muscarinic / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism
D007295:Inositol Phosphates; D010277:Parasympathomimetics; D010716:Phosphatidylinositols; D011976:Receptors, Muscarinic; D001285:Atropine; D002217:Carbachol; D008094:Lithium; D010738:Type C Phospholipases