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Muscarinic Receptors and Hydrolysis of Inositol Phospholipids in Rat Cerebral Cortex and Parotid Gland
Author(s) -
Jacobson Michael D.,
Wusteman Monica,
Downes C. Peter
Publication year - 1985
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1985.tb05437.x
Subject(s) - muscarinic acetylcholine receptor , inositol , cerebral cortex , receptor , chemistry , neuroscience , parotid gland , endocrinology , inositol phosphate , medicine , biochemistry , biology , pathology
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 [ 3 H]inositol, this response could be monitored by measuring the formation of [ 3 H]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 m M ) in the medium completely blocked the hydrolysis of inositol 1‐phosphate, partially inhibited inositol 1,4bisphosphate 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 [ 3 H]inositol 1‐phosphate in the presence of 10 m M 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.