Participation of a proton-cotransporter, MCT1, in the intestinal transport of monocarboxylic acids.
A molecular mechanism for the intestinal monocarboxylic acid transport was characterized by using a proton/monocarboxylate transporter, MCT1, in Chinese hamster ovary (CHO) cells, first found by Garcia et al. (Cell, 76, 865-873, 1994). Northern blotting analysis showed that MCT1-isomers exist in the rat and rabbit intestinal enterocytes and Caco-2 cells. The expression of [14C]lactic acid uptake by Xenopus laevis oocytes injected with rabbit intestinal mRNA was reduced by hybridizing the mRNA with a MCT1 cDNA of CHO cells before microinjection used as the antisense DNA. [14C]Lactic acid uptake by CHO cells was pH dependent, saturable, stereospecific, and reduced in the presence of acetic acid, benzoic acid, S- and R-ibuprofen, S- and R-mandelic acid, nicotinic acid, pravastatin, propionic acid and valproic acid. In addition, several monocarboxylic acids were transported in pH-dependent and saturable manners. These results suggest that the intestinal MCT1-related protein contributes to a carrier-mediated absorption for organic weak acid compounds.
Tamai
I
I
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, School of Medicine, Kanazawa University, Japan.
Takanaga
H
H
Maeda
H
H
Sai
Y
Y
Ogihara
T
T
Higashida
H
H
Tsuji
A
A
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D016466:CHO Cells; D002264:Carboxylic Acids / Q000378:metabolism*; D002352:Carrier Proteins / Q000096:biosynthesis / Q000378:metabolism*; D006224:Cricetinae; D005260:Female; D006863:Hydrogen-Ion Concentration; D007052:Ibuprofen / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism*; D007773:Lactates / Q000378:metabolism; D008333:Mandelic Acids / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism; D027501:Monocarboxylic Acid Transporters; D009525:Niacin / Q000378:metabolism / Q000494:pharmacology; D009865:Oocytes / Q000502:physiology; D017035:Pravastatin / Q000494:pharmacology; D011422:Propionates / Q000494:pharmacology; D011522:Protons; D018075:RNA, Complementary; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D011994:Recombinant Proteins / Q000378:metabolism; D013237:Stereoisomerism; D014158:Transcription, Genetic; D014162:Transfection; D014635:Valproic Acid / Q000494:pharmacology; D014982:Xenopus laevis
D002264:Carboxylic Acids; D002352:Carrier Proteins; D007773:Lactates; D008333:Mandelic Acids; D008565:Membrane Proteins; D027501:Monocarboxylic Acid Transporters; D011422:Propionates; D011522:Protons; D018075:RNA, Complementary; D012333:RNA, Messenger; D011994:Recombinant Proteins; D009525:Niacin; D014635:Valproic Acid; C029658:propionic acid; D017035:Pravastatin; C037938:mandelic acid; D007052:Ibuprofen