The renal basolateral transport system for organic anions: properties of the regulation mechanism.
The aim of the present study was to investigate whether the activity of the renal basolateral transport system for organic anions is modulated by protein kinase C (PKC). The studies were performed on isolated nonperfused S2 segments of proximal tubules, microdissected from rabbit kidneys without the use of enzymatic agents. Several PKC-activating substances and staurosporine, a PKC inhibitor, were added to the incubation solution containing 3H-PAH at 6.5 x 10(-7) M as a marker substance for the basolateral anion transporter. The phorbol ester phorbol 12-myristate 13-acetate showed dose-dependent effects on the tubular PAH uptake, inducing a 2-fold increase in the PAH transport rate compared with control at a concentration of 10(-7) M. Oleyl-2-acetylglycerol, a membrane permeant analog of the physiological PKC activator diacylglycerol, had similar effects, but the maximum stimulating concentration was 10(-5) M. The shift to higher concentrations might be due to an intracellular metabolization of oleyl-2-acetylglycerol. In addition, myoinositol, a precursor of the PKC-activating pathway, induced a 2-fold increase in PAH accumulation at a concentration of 10(-5) M. These effects were abolished by the administration of staurosporine at low concentrations (10(-9) and 10(-8) M). Staurosporine on its own diminished the PAH uptake in a concentration-dependent manner at bath concentrations ranging from 10(-7) to 10(-5) M. We conclude that the PKC system may be an important modulator of the basolateral PAH transport in renal S2 proximal tubules.
Hohage
H
H
Department of Pharmacology and Toxicology, Rheinisch-Westfälische Technische Hochschule Aachen, Federal Republic of Germany.
Löhr
M
M
Querl
U
U
Greven
J
J
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D000838:Anions / Q000378:metabolism*; D004075:Diglycerides / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D066298:In Vitro Techniques; D007294:Inositol / Q000494:pharmacology; D017136:Ion Transport / Q000502:physiology; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011817:Rabbits; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010130:p-Aminohippuric Acid / Q000493:pharmacokinetics
D000470:Alkaloids; D000838:Anions; D004075:Diglycerides; D007294:Inositol; C038237:1-oleoyl-2-acetylglycerol; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate; D010130:p-Aminohippuric Acid