Carrier-mediated uptake of nicotinic acid by rat intestinal brush-border membrane vesicles and relation to monocarboxylic acid transport

J Pharmacobiodyn. 1990 May;13(5):301-9. doi: 10.1248/bpb1978.13.301.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport
  • Carboxylic Acids / pharmacokinetics*
  • Carboxylic Acids / pharmacology
  • Extracellular Space / metabolism
  • Hydrogen-Ion Concentration
  • Intestinal Absorption
  • Intestine, Small / metabolism
  • Intestine, Small / ultrastructure
  • Kinetics
  • Male
  • Membrane Potentials / physiology
  • Membranes / metabolism
  • Microvilli / metabolism*
  • Microvilli / ultrastructure
  • Niacin / pharmacokinetics*
  • Osmolar Concentration
  • Rats
  • Rats, Inbred Strains
  • Sodium / pharmacology


  • Carboxylic Acids
  • Niacin
  • Sodium