THE IRREVERSIBLE BINDING OF ACETYLCHOLINE MUSTARD TO MUSCARINIC RECEPTORS IN INTESTINAL SMOOTH MUSCLE OF THE GUINEA‐PIG

Abstract

1 Acetylcholine mustard (N-2-chloroethyl-N-methyl-2-acetoxyethylamine), a potent muscarinic agonist, binds virtually irreversibly to muscarinic receptors in longitudinal muscle strips from guinea-pig small intestine, as shown by the inhibition of the binding of [³H]-propylbenzilylcholine mustard ([³H]-PrBCM), an affinity label for the muscarinic receptor. 2 A value for the apparent binding affinity of acetylcholine mustard and a value for the rate constant for the receptor alkylation reaction have been deduced from the rate of onset of the inhibition of [³H]-PrBCM binding. 3 The kinetic constants obtained may refer largely to the interaction between acetylcholine mustard and the desensitized receptor. 4 At high concentrations acetylcholine mustard practically abolishes the contractile response to carbachol. At these concentrations acetylcholine mustard appears to have multiple actions on the tissue.