Carrier-Mediated Uptake of Nicotinic Acid by Rat Intestinal Brush-Border Membrane Vesicles and Relation to Monocarboxylic Acid Transport

Matheus Timbul Simanjuntak, Ikumi Tamai, Tetsuya Terasaki, Akira Tsuji

Research output: Contribution to journalArticlepeer-review

59 Citations (Scopus)

Abstract

The intestinal transport of [14C] nicotinic acid was investigated at 27 °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 extra-vesicular 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.

Original languageEnglish
Pages (from-to)301-309
Number of pages9
Journaljournal of pharmacobio-dynamics
Volume13
Issue number5
DOIs
Publication statusPublished - 1990

Keywords

  • active transport
  • brush-border membrane vesicle
  • carrier-mediated transport
  • intestinal uptake
  • monocarboxylic acid
  • nicotinic acid
  • proton dependent transport
  • vitamin

ASJC Scopus subject areas

  • Pharmacology

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