title: The renal basolateral transport system for organic anions: properties of the regulation mechanism.
abstract: 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.
authors.affiliation: Department of Pharmacology and Toxicology, Rheinisch-Westfälische Technische Hochschule Aachen, Federal Republic of Germany.
authors.forename: H
authors.initials: H
authors.lastname: Hohage
authors.forename: M
authors.initials: M
authors.lastname: Löhr
authors.forename: U
authors.initials: U
authors.lastname: Querl
authors.forename: J
authors.initials: J
authors.lastname: Greven
mesh_terms: 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
chemical_list: 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