Carrier-mediated uptake of nicotinic acid by rat intestinal brush-border membrane vesicles and relation to monocarboxylic acid transport.
The intestinal transport of [14C]nicotinic acid was investigated at 27 degrees C by using brush-border membrane vesicles (BBMV) isolated from the rat small intestine. The osmolarity sensitive uptake by BBMV showed a remarkable overshoot phenomenon in the presence of an inward-directed H+ gradient (pHin = 7.5, pHout = 6.0). In contrast, the imposition of a Na+ gradient ([Na+]in = 0 mM, [Na+]out = 100 mM) had no stimulatory effect on the uptake of [14C]nicotinic acid. The remarkable pH-dependence of the initial uptake showing an increase of the uptake rate with decreasing the extravesicular pH disappeared completely in the presence of a structural analogue, isonicotinic acid, at pH below 6.5. In the presence of a H+ gradient, the initial uptake of [14C]nicotinic acid was saturable with the apparent Kt of 4.43 mM and Jmax of 2.55 nmol/mg protein/15 s. The uptake was increased by the imposition of an inside-positive membrane potential and was significantly inhibited by monocarboxylic acids such as benzoic acid, salicylic acid, acetic acid, propionic acid, valproic acid and L-lactic acids as well as two isomers (isonicotinic acid and picolinic acid). The uptake was not inhibited by nicotinamide, nicotinyl alcohol, D-glucose, p-aminohippuric acid, glycyl-L-proline, succinic acid and an exchange transport inhibitor. From these results it was concluded that nicotinic acid is transported through the intestinal brush-border membrane by a carrier-mediated system and the system can recognize some acidic drugs with a monocarboxylic group. The pH dependent intestinal uptake of nicotinic acid can be ascribed to the proton-coupled and active carrier-mediated transport mechanism rather than a simple diffusion of the undissociated nicotinic acid to follow a pH-partition hypothesis.
Simanjuntak
M T
MT
Faculty of Pharmaceutical Sciences, Kanazawa University, Japan.
Tamai
I
I
Terasaki
T
T
Tsuji
A
A
D000818:Animals; D001692:Biological Transport; D002264:Carboxylic Acids / Q000493:pharmacokinetics* / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption; D007421:Intestine, Small / Q000378:metabolism / Q000648:ultrastructure; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008566:Membranes / Q000378:metabolism; D008871:Microvilli / Q000378:metabolism* / Q000648:ultrastructure; D009525:Niacin / Q000493:pharmacokinetics*; D009994:Osmolar Concentration; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000494:pharmacology
D002264:Carboxylic Acids; D009525:Niacin; D012964:Sodium