Acid-Base Effects on Renal Organic Cation Transport 1

Abstract

Mammalian renal tubules secrete strong organic cations such as tetraethylammonium (TEA), N'-methylnicotinamide and mepiper-phenidol (Darstine) by a common route which is functionally distinct from the transport system for organic anions. Because of profound pharmacologic responses which may occur upon administration of some of these organic cations, many studies of this secretory transport pathway have been performed in vitro (2-4). While several parameters of this transport have been studied, little is known concerning the effects of acid-base balance upon it. The present study was conducted to determine how intracellular and extracellular factors in acidosis and alkalosis affect TEA transport in renal slices and to compare these observations with previous observations of hippurate transport (5).

Materials and Methods. Male Sprague-Dawley rats, 150-250 g, were used in all experiments. Rats were allowed free access to chow and drank water, NH₄Cl solution (1.0% w/v), or NaHCO₃ solution (1.5% w/v). The latter two solutions were drunk for a period of 7 to 10 days.

Rats were sacrificed by a blow to the head, the kidneys were rapidly removed and placed in cold saline. Cortical slices (0.4 to 0.5 mm) were cut with a Stadie-Riggs microtome (6) within the subsequent 30 min.

The basic incubation medium used was that described by Cross and Taggart (7) phosphate buffered sodium, potassium and chloride solution. To this, we added ¹⁴C-tetraethyl-ammonium bromide (TEA) (New England Nuclear) at a concentration of 10^-5 M. In a few studies, ¹³¹I-Na iodo hippurate at a concentration of 10^-5 M was added. Medium pH was 7.4; however, in some studies, 0.1 N HCl or 0.1 N NaOH was added to the medium to obtain a range of pH. Following 90 min of incubation at 24° on a Dubnoff shaker, slices were removed, blotted and weighed.