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.
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.
Simanjuntak
M T
MT
Faculty of Pharmaceutical Sciences, Kanazawa University, Japan.
Terasaki
T
T
Tamai
I
I
Tsuji
A
A
D000085:Acetates / Q000493:pharmacokinetics*; D019342:Acetic Acid; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D001693:Biological Transport, Active; D005227:Fatty Acids / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007421:Intestine, Small / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008871:Microvilli / Q000378:metabolism; D009994:Osmolar Concentration; D011817:Rabbits; D012459:Salicylates / Q000494:pharmacology; D020156:Salicylic Acid
D000085:Acetates; D001639:Bicarbonates; D005227:Fatty Acids; D012459:Salicylates; D020156:Salicylic Acid; D019342:Acetic Acid