Kinetics of the in Vitro Binding of a Quaternary Ammonium Compound (p-Biphenylmethyl-(dl-tropyl-α-tropinium) bromide (BTTB)) to Lysosomes and Other Subcellular Membranes of Rat Liver
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概要
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The extent of binding of tritiated p-biphenylmethyl-(dl-tropyl-α-tropinium) bromide (^3H-BTTB) to subcellular membranes was investigated by the centrifugal method. The following results were obtained. 1. The binding was apparently independent of enzymatic reactions. 2. The binding of BTTB to lysosomal membranes gave a linear Lineweaver-Burk plot with an apparent K_m=4.3μM and V_<max>=0.25 nmol・mg protein^<-1>・min^<-1>. N-Methylatropinium bromide competitively reduced the affinity of BTTB to lysosomal membranes. 3. Inhibitory effects on the binding of BTTB with lysosomal membranes were observed with choline, acetylcholine. anisotropine (quaternary ammonium compounds), quinacrine and chloroquine (tertiary amine compounds). Cetrimonium bromide (CTAB), ethidium bromide, indocyanine green, hexamethonium succinylcholine, all structurally unrelated ammonium compounds, also showed significant inhibitory effects. 4. Incubation of lysosomal membranes with increasing concentrations of indocyanine green resulted in a dose-related inhibition of the binding of ^3H-BTTB. The binding of ^3H-BTTB to lysosomal membranes was significantly decreased by the addition of choline at concentrations of 1 and 0.1 mM, and also by the addition of acetylcholine at a concentration of 1 mM. Methacholine and carbachol caused no change in the binding of ^3H-BTTB at any concentration tested. Thus, amines and quaternary ammonium compounds competitively inhibit the binding of BTTB to lysosomal membranes by virtue of their strong affinity for lysosomes rather than because of the similarity of their structures to that of BTTB, a basic compound with affinity for lysosomes.
- 公益社団法人日本薬学会の論文
- 1984-04-25
著者
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須賀 哲弥
Department of Clinical Biochemistry, Tokyo College of Pharmacy
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須賀 哲弥
東京薬科大学
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松本 善雄
Department of Clinical Biochemistry, Tokyo College of Pharmacy
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松本 善雄
Department Of Clinical Biochemistry Tokyo College Of Pharmacy
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須賀 哲弥
Department Of Clinical Biochemistry Tokyo College Of Pharmacy
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