디벤아민에 의한 무스카린 수용체 아형의 불활성화

Inactivation of the Muscarinic Receptor Subtype by Dibenamine

Dibenamine inhibited [3H]quinuclidinyl benzilate ([3H]QNB) binding in both concentration and incubation time-dependent manners. The IC50 value of dibenamine for the inhibition of the specific binding of 100pM [3H]QNB following incubation of cerebral microsomes with dibenamine at 37oC for 15 min was 20mcM. Dibenamine irreversibly decreased the binding site concentration for [3H]QNB binding without affecting the affinity of [3H]QNB for the muscarinic receptor. Analysis of the pirenzepine inhibition curve of [3H]QNB binding to cerebral microsomes indicated the presence of two receptor subtypes with high (M1 receptor, Ki=5nM) and low (M2 receptor. Ki=l6OnM) affinity for pirenzepine. However, dibenamine(20mcM) treatment under the condition employed in these experiments caused steepening of the pirenzepine competition curve. The Ki value for pirenzepine in dibenamine treated microsomes was approximately 120nM, suggesting a selective decrease in the number of Ml receptor. Although dibenamine also inhibited [3H]QNB binding to ventricular microsomes with the IC50 value of 120mcM, the sensitivity for dibenamine in the ventricle was much lower than that in the cerebrum. These results indicate that dibenamine at low concentrations selectively inactivates the muscarinic M1 receptor.