Differential desensitization of muscarinic receptor-stimulated phosphoinositide turnover in the rat brain.

Desensitization of the muscarinic receptor-mediated phosphoinositide (PI) turnover response in the striatum and cortex of the rat brain was examined. The rate of accumulation of inositol phosphates during carbachol-stimulated PI turnover was constant for at least 60 min in the cortex, but decreased with time in the striatum. The effects of preincubation in the presence of the muscarinic agonist carbachol on muscarinic receptor-mediated PI turnover in slices and subsequent receptor binding in cell aggregates prepared from the slices were measured. Preincubation of striatal tissue produced a significant and sustained loss of responsiveness, which reached a minimum after 2 h; whereas, a transient and much weaker loss of responsiveness was observed in the cortex. Preincubation did not affect the number of muscarinic receptors as measured by the binding of [ (3)H ]l- quinuclidinyl benzilate or [ (3)H ]N- methylscopolamine in either cortex or striatum. The data suggest that the muscarinic receptor-stimulated PI turnover response can be more readily desensitized in striatum compared with cortex.