PMID: 9428572Jan 1, 1997Paper

Muscarinic M1 and M3 receptors in rat striatum: a binding study

Archives of Medical Research
M T de la VegaJ A Arias-Montaño

Abstract

In this study, the authors set out to determine the presence of M3 muscarinic receptors in rat striatum by examining the binding of [3H]N-methylscopolamine ([3H]NMS) to striatal membranes and its displacement by antagonists with different affinity for M1 and M3 muscarinic receptors -pirenzepine; 4-diphenylacetoxy-N-methylpiperidine methiodide, 4-DAMP; and the p-fluoro analog of hexahydro-sila-difenidol, pFHHSiD). The specific binding of [3H]NMS to membranes from rat striatum (551 +/- 40 fmol.mg prot.-1, KD 0.11 +/- 0.01 nM) was displaced in a concentration-dependent manner by all three antagonists tested. Inhibition curves best fit to a single-site model for 4-DAMP (pKi 9.1 +/- 0.1), whereas for both pirenzepine and pFHHSiD, the best fit was to the two-site model. The pKi values for the high-affinity (8.0 +/- 0.2) and low-affinity (6.7 +/- 0.2) components for pirenzepine-mediated inhibition of [3H]NMS binding corresponded to those reported for M1 and M3 receptors, respectively. The pKi values for the high-affinity (7.7 +/- 0.1) and low-affinity (7.1 +/- 0.2) components for pFHHSiD inhibition were in good agreement with those reported for M3 and M1 receptors, respectively. Altogether, these results indicate the presence in rat s...Continue Reading

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