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Interaction of benzilylcholine mustard, benzilylcholine and lachesine with the histamine receptor in the longitudinal muscle of guinea‐pig ileum
Author(s) -
REASBECK P. G.,
YOUNG J. M.
Publication year - 1973
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1973.tb08233.x
Subject(s) - muscarinic acetylcholine receptor , mepyramine , histamine , chemistry , atropine , receptor , dissociation constant , endocrinology , ileum , medicine , biophysics , biology , biochemistry , antagonist
Summary1 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 × 10 −8 M) afforded complete protection for the histamine receptor against the effects of BCM. 2 Recovery from block at 30° 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 × 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.