Regulation of Brain Muscarinic Receptors by Protein Kinase C
Final rept. May 1988-Jun 1991
MARYLAND UNIV BALTIMORE DEPT OF PHARMACOLOGY AND TOXICOLOGY
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We investigated the pharmacological classification of the subtypes of muscarinic receptors which are coupled to increased hydrolysis of phosphoinositides in rat cerebral cortex. Our results indicated that both M1 and M3 receptors mediate such a response. This response to muscarinic receptor simulation is partially blocked by tetrodotoxin or by protein kinase C activators. The component of the response that is sensitive to blockade by such agents does not correspond to a certain receptor subtype. We investigated the role of protein kinase C in desensitization of muscarinic receptor function in a neuronal clone. While this kinase was clearly involved in the effects of phorbol esters, it did not play a role in agonist-induced receptor desensitization. We also studied some of the molecular events which accompany muscarinic receptor desensitization and down-regulation. These studies indicated that prolonged in vivo treatment of rats with an irreversible acetylcholinesterase decreased the concentration of the mRNA encoding the M2 muscarinic receptor.
- Medicine and Medical Research