Intestinal brush-border membrane transport of monocarboxylic acids mediated by proton-coupled transport and anion antiport mechanisms.
Intestinal brush-border membrane transport of monocarboxylic acids was investigated by using rabbit intestinal brush-border membrane vesicles (BBMVs) and isolated intestinal tissues mounted on Ussing-type chambers. [3H]Mevalonic acid uptake by BBMVs showed an overshoot phenomenon in the presence of an inwardly directed proton gradient, but not in the presence of an inwardly directed sodium gradient or an outwardly directed HCO3- or chloride gradient. Initial uptake of mevalonic acid was saturable in the presence of a proton gradient. Uptake of [3H]mevalonic acid was inhibited by various monocarboxylic acids, including acetic acid, benzoic acid, lactic acid, nicotinic acid, pravastatin, salicylic acid and valproic acid, but not by dicarboxylic acid or amino acids. Acetic acid, which is transported by both anion antiport and proton-coupled transport systems, induced serosal bicarbonate-dependent alkalinization in the mucosal-side bathing solution of rabbit jejunal tissues, when examined in Ussing-type chambers. Pravastatin, which is a structural analogue of mevalonic acid and is absorbed via proton-coupled transport like mevalonic acid, did not. The result demonstrates that acetic acid is transported by the bicarbonate-dependent anion antiport system, whereas pravastatin is not. So, it is suggested that monocarboxylic acids are transported by at least two independent transporters, namely, a proton-coupled transporter for most monocarboxylic acids, including mevalonic acid, pravastatin and acetic acid, and an anion antiporter for acetic acid, but not for mevalonic acid or pravastatin. Activation of anion antiporter can induce HCO3- secretion in intact intestine.
Tamai
I
I
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kanazawa University, Japan.
Takanaga
H
H
Maeda
H
H
Yabuuchi
H
H
Sai
Y
Y
Suzuki
Y
Y
Tsuji
A
A
D019342:Acetic Acid / Q000493:pharmacokinetics; D000818:Animals; D017920:Antiporters / Q000502:physiology*; D001565:Benzoates / Q000493:pharmacokinetics; D019817:Benzoic Acid; D001639:Bicarbonates / Q000378:metabolism; D001692:Biological Transport; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000648:ultrastructure; D008798:Mevalonic Acid / Q000493:pharmacokinetics*; D008871:Microvilli / Q000378:metabolism; D017035:Pravastatin / Q000493:pharmacokinetics; D011522:Protons; D011817:Rabbits
D017920:Antiporters; D001565:Benzoates; D001639:Bicarbonates; D011522:Protons; D019817:Benzoic Acid; D017035:Pravastatin; D019342:Acetic Acid; D008798:Mevalonic Acid