POSTNATAL-DEVELOPMENT OF MUSCARINIC RECEPTOR-STIMULATED PHOSPHOINOSITIDE METABOLISM IN MOUSE CEREBRAL-CORTEX - SENSITIVITY TO ETHANOL

An enhanced coupling of cholinergic muscarinic receptors to phosphoino sitide metabolism had been previously observed in brain from immature rat. This study reports that the postnatal development of muscarinic r eceptor-stimulated phosphoinositide metabolism is also enhanced in cer ebral cortex slices from immature Swiss-Webster and Balb-c mice, as co mpared to adults. Response to the agonist carbachol was lower on postn atal day 3, peaked between days 5 and 12 and then declined to adult le vels. Density of muscarinic binding sites, measured with the M(1) liga nd [H-3]telenzepine on postnatal day 7, was, on the other hand, only h alf of the adult value. Phosphoinositide hydrolysis stimulated by glut amate decreased with age, while that elicited by norepinephrine increa sed. These results are also similar to those previously reported in th e rat. Ethanol has been found to inhibit muscarinic receptor-stimulate d phosphoinositide metabolism in rat brain in an age-dependent manner. This was confirmed in mouse brain, where ethanol inhibited this respo nse in cerebral cortex of immature but not adult animals. These result s indicate that the enhanced muscarinic receptor-stimulated phosphoino sitide metabolism, which coincides with the brain growth spurt, is sim ilar in rats and mice. Mice may be a useful species in which to geneti cally manipulate muscarinic receptors to gain a better understanding o f their potential role in brain development.