Abstract
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.
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