Ontogeny of cortical muscarinic receptor subtypes and muscarinic receptor-mediated responses in rat.

To determine the ontogenetic relationship of muscarinic receptor and effector systems in the central nervous system, the developmental time courses for binding sites with high (M1) and low (M2) affinity for pirenzepine as well as muscarinic receptor-mediated stimulation of phosphoinositide breakdown and inhibition of cyclic AMP accumulation were examined in rat cortex. M1 sites were 30% of adult levels at 1 week, 70% at 2 weeks, 90% at 3 weeks and equal to adult levels at 4 weeks postpartum. M2 sites, on the other hand, did not show a significant change between the ages of 1 and 6 weeks. Acetylcholine-stimulated phosphoinositide breakdown was detected at all ages tested (1, 2, 3, 4 and 6 weeks). The percentage of conversion of [3H] phosphoinositides to [3H]inositol phosphates, stimulated by 1 mM acetylcholine, increased with age until 3 weeks after birth and then decreased slightly at ages 4 and 6 weeks. Carbachol inhibition of [3H]cyclic AMP accumulation, on the other hand, was undetectable in tissues from 1- and 2-week-old rats, whereas in tissues from 3- and 4-week-old rats, the responses were at 6-week level. Thus, for carbachol inhibition of cyclic AMP accumulation, a time in development existed (2 weeks after birth) at which receptors appeared to be present but response to stimulation was absent. To examine indirectly the coupling of binding sites to second messenger systems via guanine nucleotide-binding regulatory proteins, the density of binding sites for the muscarinic receptor agonist, [3H]oxotremorine-M, was measured.(ABSTRACT TRUNCATED AT 250 WORDS)