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Muscarinic acetylcholine receptors purified from porcine cerebrum (predominantly M1 subtype) and porcine atrium (M2 subtype) showed essentially the same affinity for any given antagonist, including pirenzepine. This is in contrast with the difference in the affinity for pirenzepine between cerebral and atrial receptors in native membranes, and with that between mAChR I (M1) and mAChR II (M2) receptor subtypes expressed in Xenopus oocytes. Purified atrial receptors showed heterogeneous affinities for acetylcholine but a single homogeneous affinity for oXotremorine, pilocarpine and carbachol, in contrast with purified cerebral receptors, which showed heterogeneous affinities for all these agonists. The dissociation constants for the binding of acetylcholine with high-and low-affinity sites in atrial receptor preparations were essentially the same as those in the cerebral receptors; dissociation constants for the binding of oxotremorine, pilocarpine and carbachol with atrial receptors were similar to those in the low-affinity sites of cerebral receptors. The affinity for carbachol of atrial receptors increased 17-fold on treatment with 5,5'-dithiobis(2-nitrobenzoic acid), and their affinities for [3H]QNB, pirenzepine and carbachol decreased on treatment with dithiothreitol, the findings which resemble the effects of these sulfhydryl agents on cerebral receptors. These results suggest that the ligand-binding domains of the M1 and M2 receptor proteins are similar to each other and are regulated by the redox state of cysteine residues common to the two proteins, but the interaction of receptor proteins with membrane components is required for their subtype-specific interaction with pirenzepine. I4a

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