Participation of Monocarboxylic Anion and Bicarbonate Exchange System for the Transport of Acetic Acid and Monocarboxylic Acid Drugs in the Small Intestinal Brush-Border Membrane Vesicles
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概要
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A participation of bicarbonate exchange system for the transport of acetic acid and the related monocarboxylic acid drugs in the intestinal brush-border membrane vesicles (BBMVs) was investigated. The uptake of [^3H] acetic acid at 37℃ by BBMVs was markedly stimulated and showed a clear overshoot phenomenon in the presence of outward-directed bicarbonate gradient (pH_<in> = 7.5,[KHCO_3]_<in> or [NaHCO_3]_<in> = 100 mM ; pH_<out> = 7.5,[K-gluconate]_<out> or [Na-gluconate]_<out> = 100 mM). This uptake process was saturable (K_t = 50.4±4.96 mM and J_<max> = 11.6±0.61 nmol/mg protein/10 s) and was inhibited by DIDS (4,4-diisothiocyano-2,2'-disulfonic acid stilbene disodium salt) and furosemide, anion exchange inhibitors, and by many monocarboxylates. The initial uptake of [^3H] acetic acid was competitively inhibited by salicylic acid, suggesting the common transport between acetic acid and salicylic acid. At lower extravesicular pHs and in the presence of outward-directed bicarbonate gradient (pH_<in> = 7.5,[KHCO_3]_<in> = 100 mM ; pH_<out> = 6.0 or 5.0,[K-gluconate]_<out> = 100 mM) where membrane potential was clamped to zero by K^+-valinomycin, the uptake of [^3H] acetic acid showed an overshoot phenomenon, whereas the uptake was significantly decreased in the presence of carbonyl cyanide p-trifluoromethoxyphenylhydrazone, a protonophore. It was concluded, therefore, that there are one or two mechanisms for the carrier-mediated transport of acetic acid and monocarboxylates related to bicarbonate exchange systems in rabbit intestinal BBMVs : 1) proton gradient independent and bicarbonate exchange system ; 2) proton gradient dependent and bicarbonate exchange system.
- 公益社団法人日本薬学会の論文
著者
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Tsuji Akira
Faculty Of Pharmaceutical Sciences Kanazawa University
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Tsuji Akira
金沢大学 薬
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Tsuji Akira
富山化学工業綜合研究所
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TERASAKI Tetsuya
Faculty of Pharmaceutical Sciences, Kanazawa University
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Tsuji A
Kanazawa Univ. Ishikawa Jpn
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Tamai I
Tokyo Univ. Sci. Tokyo Jpn
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Tamai Ikumi
Meiji Seika Kaisha Ltd. Pharmaceutical Research Center:department Of Surgery Kawasaki City Ida Hospi
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Tamai Ikumi
Faculty Of Pharmaceutical Sciences Tokyo University Of Science
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Tamai Ikumi
Department Of Pharmaceutics Faculty Of Pharmaceutical Sciences Kanazawa University
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Tamai Ikumi
Faculty Of Pharmaceutical Sciences And Hospital Pharmacy Kanazawa University
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Tsuji Akira
Department Of Pediatrics:hospital Pharmacy:and Faculty Of Pharmaceutical Sciences University Of Kana
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SIMANJUNTAK Matheus
Faculty of Pharmaceutical Sciences, Kanazawa University
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Terasaki Tetsuya
Faculty Of Pharmaceutical Sciences Kanazawa University
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Simanjuntak Matheus
Faculty Of Pharmaceutical Sciences Kanazawa University
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