항 Histamine제와 Muscarinic Recepter와의 상호작용(I) 심장 muscarinic recepter에 대한 작용

Interaction of Antihistaminics with Muscarinic Receptor(I) Action on the cardiac muscarinic receptor

[3H] Quinuelidinyl benzilate(QNB) binding assays were performed in the dog ventricular sarcolemma fraction enriched approx. 32-fold in sarcolemma compared to the starting homogenate to elucidate the effect of antihistaminics on cardiac muscarinic receptor. Chlorpheniramine(CHP) inhibited specific binding of [3H]QNB and delayed the equilibrium binding. The rate constants at 37oC for formation and dissociation of the QNB receptor complex were 0.38 X 1O9M-1min-1 and 1.6 X 1O-2min-1, respectively. The mean value for the dissociation constant from the pairs of the rate constants was 43.2pM and this value was similar to the value(44.8pM) determined from Scatchard analysis. CHP decreased association rate constant, indicating increase in KD value. Decrease in affinity without affecting the binding site concentration(Bmax) for [3H]QNB binding by CHP was also demonstrated by Scatchard analysis. Ki values for H1-blockers that inhibited specific [3H]QNB binding were 0.02-4.8mcM. Cimetidine with Ki value of 230mcM, however, was ineffective in displacing [3H]QNB binding at concentration of 50mcM. The Hill coefficient for H1-blockers were about one. The results indicate that H1-antihistaminics inhibit [3H]QNB binding by interaction with myocardiac muscarinic cholinergic recepter and anticholinergic side effects of these drugs are mainly due to this recepter blocking mechanism.