CARBACHOL STIMULATES INOSITOL PHOSPHATE FORMATION IN RAT THALAMUS SLICES THROUGH MUSCARINIC M(3)-RECEPTOR ACTIVATION

In cross-chopped slices from rat thalamus and in the presence of 10 mM LiCl, the cholinergic agonist carbachol stimulated the accumulation o f total [H-3]inositol phosphates ([H-3]IPs = [H-3]IP1 + [H-3]IP2 + [H- 3]IP3). Best-fit values for the concentration-response curve for carba chol after 60 min incubation yielded an EC(50) of 44 +/- 6 mu M, maxim um effect of 199 +/- 6% of basal accumulation and Hill coefficient (n( H)) of 1.1 +/- 0.1. Carbachol-induced [H-3]IPs accumulation was inhibi ted by 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP; pK(i) 9.1) and the p-fluoro analogue of hexahydro-sila-difenidol (pF-HHSiD; pK(i) 8.1). Concentration-response curves for carbachol were shifted t o the right in a parallel fashion by pirenzepine (100, 300 and 1000 nM ). A Schild plot of the data was linear (slope 0.95 +/- 0.04) and yiel ded a log K-D for pirenzepine of -6.8 + 0.1. Taken together, these res ults suggest that carbachol-induced inositol phosphate accumulation in rat thalamus is mediated by muscarinic M(3)-receptors.