Stimulatory action of verapamil on transport of organic acids in rat kidney cortical slices.
Effect of verapamil on the organic acid transport was examined with rat kidney cortical slices. Verapamil increased the initial rate of p-aminohippurate (PAH) uptake, markedly enhanced its maximal accumulation under steady-state conditions and depressed the efflux of PAH. The accumulation of urate was also stimulated by verapamil. D600, a derivative of verapamil, showed the same effect as verapamil with regard to the stimulation of PAH accumulation. Kinetic studies revealed that verapamil resulted in an increase in the Vmax of the transport of PAH. The apparent Km remained essentially constant. The PAH accumulation was enhanced by aerobic preincubation of the slices with verapamil at 37 degrees C. On the other hand, the preincubation of the slices with verapamil at 0 degrees C did not alter the PAH accumulation. Oxygen consumption and ATP content in the slices and microsomal (Na+ + K+)adenosine triphosphatase activity were not affected by verapamil. Verapamil enhanced a Na+ gradient to some degree. however, the PAH accumulation in the presence of verapamil and ouabain was increased approximately the same amount as in the absence of these drugs regardless of the dissipation of the Na+ gradient by ouabain. These results suggest that verapamil accumulated by the slices stimulates the PAH uptake and its stimulatory action cannot be explained by the increase in the Na+ gradient and stimulation of (Na+ + K+)adenosine triphosphatase activity.
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002264:Carboxylic Acids / Q000378:metabolism*; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008861:Microsomes / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology*; D010130:p-Aminohippuric Acid / Q000378:metabolism
D002264:Carboxylic Acids; D000255:Adenosine Triphosphate; D012964:Sodium; D014700:Verapamil; D000251:Adenosine Triphosphatases; D010130:p-Aminohippuric Acid