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The action of p-chloromercuribenzoate (PCMB) on the ligand binding properties of the muscarinic receptors in the rat cerebral cortex has been examined. At low concentrations, PCMB produces a selective change in the binding of agonists without any effect on the binding of antagonists. At higher concentrations, the structure-binding profile for binding antagonists is changed. The affinity of agonists is greatly reduced and the heterogeneity of binding eliminated. The effects of both high and low concentrations of PCMB can be reversed by dithiothreitol. Inactivation of receptors proceeds in parallel and is kinetically complex. It can only be partially reversed by dithiothreitol. Evidence is presented connecting the low affinity agonist binding site with the high affinity pirenzepine binding site. The changes produced by PCMB have been interpreted in terms of the modification of receptor conformation.
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