MUSCARINIC M-1 AND M-3 RECEPTORS IN RAT STRIATUM - A BINDING STUDY

In this study, the authors set out to determine the presence of M-3 mu scarinic receptors in rat striatum by examining the binding of [H-3]N- methyl-scopolamine ([H-3]NMS) to striatal membranes and its displaceme nt by antagonists with different affinity for M-1 and M-3 muscarinic r eceptors (pirenzepine; 4-diphenylacetoxy-N-methylpiperidine methiodide , 4-DAMP; and the p-fluoro analog of hexahydro-sila-difenidol, pFHHSiD ). The specific binding of [H-3]NMS to membranes from rat striatum (55 1+/-40 fmol.mg prot.(-1), K-D 0.11+/-0.01 nM) was displaced in a conce ntration-dependent manner by all three antagonists tested. Inhibition curves best fit to a single-site model for 4-DAMP (pK(i) 9.1+/-0.1), w hereas for both pirenzepine and pFHHSiD, the best fit was to the two-s ite model. The pK(i) values for the high-affinity (8.0+/-0.2) and low- affinity (6.7+/-0.2) components for pirenzepine-mediated inhibition of [H-3]NMS binding corresponded to those reported for M-1 and M-3 recep tors, respectively. The pK(i) values for the high-affinity (7.7+/-0.1) and low-affinity (7.1+/-0.2) components for pFHHSiD inhibition were i n good agreement with those reported for M-3 and M-1 receptors, respec tively, Altogether, these results indicate the presence in rat striatu m of both M-1 and M-3 muscarinic receptors. These findings might be re levant to the design and use of muscarinic antagonists in the treatmen t of neurological dis orders such as Parkinson's disease.