Developmental aspects of muscarinic-induced inositol polyphosphate accumulation in rat cerebral cortex

The ability of carbachol to stimulate phosphoinositide hydrolysis in developing brain was examined by assaying [3H]inositol phosphates in the presence and absence of lithium. Lithium (5 mM) enhanced carbachol-stimulated [3H]inositol monophosphate and [3H]inositol bisphosphate accumulations at every age tested but the enhancement of both [3H]inositol phosphates was greater at 7 days than at 40 days. A marked, time-dependent inhibition of [3H]inositol trisphosphate and [3H]inositol tetrakisphosphates accumulations, i.e. 29-33 and 76-79%, respectively, was produced by lithium at every age tested. Lithium also inhibited both [3H]inositol-1,3,4-trisphosphate and [3H]inositol-1,4,5-trisphosphate by 29-38%. There were no developmental differences in the EC50 values for lithium-induced potentiations of [3H]inositol mono- and bisphosphate accumulations (i.e. 0.4-0.6 and 4-6 mM, respectively). Similarly, negligible changes in the EC50 values for carbachol-induced [3H]inositol mono- and bisphosphate accumulations were observed in the presence or absence of lithium at every age tested. Models of receptor coupling and the sensitivity of inositol polyphosphate dephosphorylation to lithium block during development are considered.