Receptor reserve of phosphoinositide-coupled muscarinic receptors in mouse hippocampus in vivo

The ability of the partial muscarinic agonist pilocarpine to increase in vivo phosphoinositide. (PI) hydrolysis in mouse brain was compared to two full agonists. Pilocarpine increased in vivo phosphoinositide (PI) hydrolysis in cortex, striatum, and to the greatest extent in the hippocampus. Pilocarpine injected either subcutaneously or intracerebroventricularly robustly increased in vivo PI hydrolysis in hippocampus up to 500% of control levels and the increases were blocked by the muscarinic antagonist scopolamine. The increases in vivo PI hydrolysis induced by pilocarpine, were 60-75% of the magnitude of the full muscarinic agonists oxotremorine-M and cis-dioxolane. The muscarinic. M-1 preferring antagonist pirenzepine potently blocked pilocarpine-induced increases in in vivo PI hydrolysis, consistent with the increase being mediated by M-1 receptors. Since pilocarpine is a relatively weak partial agonist, these data suggest a substantial level of receptor reserve for the PI response in mouse hippocampus. (C) 2001 Published by Elsevier Science B.V.