Interaction of benzilylcholine mustard, benzilylcholine and lachesine with the histamine receptor in the longitudinal muscle of guinea-pig ileum.

1. The histamine receptors of longitudinal muscle strips from guinea-pig ileum were inactivated on extended exposure to concentrations of benzilylcholine mustard (BCM) above 10(-6)M. These concentrations are 3 orders of magnitude greater than those required for inactivation of the muscarinic receptors. Mepyramine (3 x 10(-8)M) afforded complete protection for the histamine receptor against the effects of BCM.2. Recovery from block at 30 degrees C was very slow with a first-order rate constant of approximately 10(-7) s(-1).3. The rate constant, k(2), for the alkylation reaction in which the reversible BCM-receptor complex is converted into an irreversible complex is much greater than the rate constant, k(-1), for dissociation of the reversible complex. The value of the rate constant, k(1), for formation of the reversible complex was 1.1 +/- 0.2 x 10(3)M(-1) s(-1).4. These observations suggested that k(1) was probably not much greater than for BCM acting on the muscarinic receptor, even though the value of k(1) was reduced by more than 2 orders of magnitude. This effect has been established for benzilylcholine and lachesine, reversible analogues of BCM. For both drugs k(1) for the histamine receptor was approximately 3 orders of magnitude less than for the muscarinic receptor, whereas k(1) was greater by a factor of only 6.