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KMID : 0043319910140020181
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Archives of Pharmacal Research
1991 Volume.14 No. 2 p.181 ~ p.187
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Interaction of Antihistaminics with Muscarinic Receptor(III) -Relationship between binding and functional in vitro data-
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Lee SW
Park YJ
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Abstract
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The muscarinic antagonist 1-[benzilic 4,4’’-3H]quinuclidinyl benzilate ([3H]QNB) bound to a single class of muscarinic receptors with high affinity in rabbit ileal membranes. The KD and Bmax values for [3H]QNB calculated from analysis of saturation isotherms were 52.5pM and 154fmol/mg, respectively. Chlorpheniramine (CHP), histamine H1 blocker, increased KDvalue for [3H]QNB without affecting the binding site concentrations and Hill coefficient. The Ki value of CHP for inhibition of [3H]QNB binding in ileal membranes was 1.44mcM and the pseudo-Hill coefficient for CHP was close to unit. In the functional assay carbachol, muscarinic agonist increased the contractile force of ileum with ED50 value of 0.11mcM. CHP caused the rightward shift of the dose-response curve to carbachol. The pA2 value of CHP determined from Schild analysis of carbachol-induced contraction was 5.77 and the slope was unity indicating competitive antagonism with carbachol. The dissociation constant (Ki) of CHP obtained in competitive experiments with [3H]QNB was similar to the KA value (1.69mcM) of CHP as inhibitor of carbachol-induced contraction in rabbit ileum. This result suggests that the binding of H1 blocker, CHP, vs [3H]QNB to muscarinic receptors in ileal membranes represents an interaction with a receptor of physiological relevance.
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