INTESTINAL UPTAKE OF NICOTINIC-ACID AS A FUNCTION OF MICROCLIMATE-PH

Abstract

The investigations aimed at clarifying the pH-dependence of 3H-nicotinic acid uptake into isolated strips of rat jejunum. Nicotinic acid is a weak-electrolyte with pKa 4.90. Thus, it was anticipated that the penetration rate of this vitamin into the intestinal epithelial cells is closely related to the amount of the diffusible i.e. non-ionic form which for its part is a function of the "virtual pH" on the mucosal surface. As determined by microelectrodes the surface pH was found to be between 5.41 and 6.80 when the strips were incubated in buffers between pH 4.5 and 9.0. At surface pH 5.83 the unidirectional flux rate was twice as high, at pH 5.41 three times as high as at surface pH values between 5.95 and 6.80. At each pH the unidirectional flux of nicotinic acid was linearly dependent on the substrate concentration in a range between 0.1 .mu.M and 1 mM, indicating simple diffusion as transport mechanism. Accordingly, the uptake rate was not affected by the substrate analogon, isonicotinic acid (5 .mu.M and 250 .mu.M). It can be concluded that the predominant part of the nicotinic acid is transported through the brush border membrane obeying the laws of a non-ionic diffusion. A relatively small portion of this substrate, however, was taken up by the tissue even when the vitamin was entirely dissociated, possibly by ionic diffusion or by binding.