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.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001561:Benzilates / Q000494:pharmacology*; D002794:Choline / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology*; D007082:Ileum / Q000187:drug effects*; D066298:In Vitro Techniques; D007700:Kinetics; D009130:Muscle, Smooth / Q000187:drug effects*; D009150:Mustard Compounds / Q000494:pharmacology*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D011955:Receptors, Drug / Q000187:drug effects*
D001561:Benzilates; D009150:Mustard Compounds; D000644:Quaternary Ammonium Compounds; D011955:Receptors, Drug; D006632:Histamine; D002794:Choline; D000109:Acetylcholine