Simanjuntak M T, Terasaki T, Tamai I, Tsuji A
Faculty of Pharmaceutical Sciences, Kanazawa University, Japan.
J Pharmacobiodyn. 1991 Sep;14(9):501-8. doi: 10.1248/bpb1978.14.501.
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 degrees C by BBMVs was markedly stimulated and showed a clear overshoot phenomenon in the presence of outward-directed bicarbonate gradient (pHin = 7.5, [KHCO3]in or [NaHCO3]in = 100 mM; pHout = 7.5, [K-gluconate]out or [Na-gluconate]out = 100 mM). This uptake process was saturable (Kt = 50.4 +/- 4.96 mM and Jmax = 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 (pHin = 7.5 [KHCO3]in = 100 mM; pHout = 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.
研究了碳酸氢盐交换系统在兔小肠刷状缘膜囊泡（BBMVs）中参与乙酸及相关一元羧酸类药物转运的情况。在37℃下，当存在外向性碳酸氢盐梯度（pHin = 7.5，[KHCO3]in或[NaHCO3]in = 100 mM；pHout = 7.5，[K - 葡萄糖酸盐]out或[Na - 葡萄糖酸盐]out = 100 mM）时，BBMVs对[3H]乙酸的摄取显著增强，并呈现明显的过冲现象。该摄取过程具有饱和性（Kt = 50.4 ± 4.96 mM，Jmax = 11.6 ± 0.61 nmol/mg蛋白质/10 s），且受到阴离子交换抑制剂4,4 - 二异硫氰基 - 2,2'-二磺酸芪二钠盐（DIDS）和呋塞米以及多种一元羧酸盐的抑制。[3H]乙酸的初始摄取受到水杨酸的竞争性抑制，这表明乙酸和水杨酸之间存在共同转运机制。在较低的囊泡外pH值且存在外向性碳酸氢盐梯度（pHin = 7.5，[KHCO3]in = 100 mM；pHout = 6.0或5.0，[K - 葡萄糖酸盐]out = 100 mM）时，通过缬氨霉素将膜电位钳制为零，[3H]乙酸的摄取呈现过冲现象，而在质子载体羰基氰化物对三氟甲氧基苯腙存在的情况下，摄取则显著降低。因此得出结论，在兔小肠BBMVs中，存在一或两种与碳酸氢盐交换系统相关的载体介导的乙酸和一元羧酸盐转运机制：1）质子梯度非依赖性和碳酸氢盐交换系统；2）质子梯度依赖性和碳酸氢盐交换系统。
