Muscarinic Receptor - Mediated Phosphoinositide Hydrolysis in Rat Brain

Objective: Activation of cholinergic muscarinic receptors leads to activation of membrane bound phospholipase C, leading to generation of IP3 and diacylglycérol, The present study aimed at measuring muscarinic receptor-mediated phosphoinositide breakdown in three different regions of rat brain. Methods: Cortical, hippocampal and striatal slices labeled with [3H] myo-inositol were incubated with muscarinic agonist carbachol (Cch) and LiCI. Reaction was terminated by the addition of chloroform/methanol and labeled inositol phosphates were extracted from tissue. Individual [3H]inositol phosphates were separated using anion exchange chromatography. Results: Cch caused a rise in IP, formation, where the increase over basal in the cortex, hippocampus and striatum were 98%, 73% and 45%, respectively. Conclusion: Phosphoinositide turnover was stimulated by carbachol in all brain structures studied, with the most pronounced effects observed in the cortex and hippocampus. Key W ords: Muscarinic receptors, inositol phosphates, carbachol, rat brain