Postnatal ontogeny of agonist and depolarization-induced phosphoinositide hydrolysis in rat cerebral cortex

Abstract

The ability of muscarinic and alpha-1 adrenoceptor agonists and elevated extracellular K+ to initiate cerebral cortical phosphoinositide hydrolysis at different stages in development was examined by prelabeling slices with [3H]inositol and assaying [3H] inositol phosphates ([3H]IPs) in the presence of lithium. Both carbachol and noradrenaline evoked an increase in [3H]IP accumulation at every age tested, although there were marked developmental differences in maximal responsiveness. Very large responses to carbachol were observed (greater than 20-fold) in the 1st week of development and these responses declined with time reaching adult levels at 21 days. During this time there was negligible change in the apparent affinity of carbachol and no effect on the relative intrinsic activity of a partial agonist arecoline. Maximal responses to noradrenaline at early ages (2, 7 and 14 days) were comparable with those observed in adult cortex but a significantly higher apparent affinity for noradrenaline and a higher relative intrinsic activity for phenylephrine were observed at these ages. Muscarinic and alpha-1 adrenoceptor binding sites increased progressively with age and reached adult levels by 21 to 40 days. Elevation of extracellular K+ to 18 mM resulted in an increased production of [3H]IPs at every age. The cholinesterase inhibitor physostigmine (50 microM) enhanced the response produced by elevated K+ at 14, 21 and 40 days but had no effect at 2 or 7 days. The Ca++ channel activator BAY-K-8644 (1 microM) enhanced the responses produced by elevated K+ at 7 and 40 days.(ABSTRACT TRUNCATED AT 250 WORDS)