Receptor reserve of phosphoinositide-coupled muscarinic receptors in mousehippocampus in vivo

The ability of the partial muscarinic agonist pilocarpine to increase in vi vo phosphoinositide. (PI) hydrolysis in mouse brain was compared to two ful l agonists. Pilocarpine increased in vivo phosphoinositide (PI) hydrolysis in cortex, striatum, and to the greatest extent in the hippocampus. Pilocar pine injected either subcutaneously or intracerebroventricularly robustly i ncreased in vivo PI hydrolysis in hippocampus up to 500% of control levels and the increases were blocked by the muscarinic antagonist scopolamine. Th e increases in vivo PI hydrolysis induced by pilocarpine, were 60-75% of th e magnitude of the full muscarinic agonists oxotremorine-M and cis-dioxolan e. The muscarinic. M-1 preferring antagonist pirenzepine potently blocked p ilocarpine-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 r eserve for the PI response in mouse hippocampus. (C) 2001 Published by Else vier Science B.V.