Regulation by protein kinase C of the contraluminal transport system for organic cations in rabbit kidney S2 proximal tubules.
In the present study the effects of structurally different stimulators of protein kinase C (PKC) (phorbolesters and oleylacetylglycerol) as well as of staurosporine, a specific inhibitor of PKC activity, on the uptake of tetraethylammonium (TEA), a maker of the renal cation transport system, was investigated on isolated S2 segments of rabbit kidney proximal tubules. Because the tubules were not perfused, and hence were collapsed, the cellular uptake of TEA reflects transport across the contraluminal membrane. The results show that the phorbolester phorbol 12-myristate 13-acetate induced a dose- and time-dependent stimulatory effect on tubular TEA uptake. The presence of extracellular chloride ions was a prerequisite for the action of phorbol 12-myristate 13-acetate on the cation transporter. The phorbolester 4 alpha-phorbol 12, 13-didecanoate also stimulated TEA uptake, but to a much lower degree than phorbol 12-myristate 13-acetate. The effects of the phorbolesters could be mimicked by oleylacetylglycerol, a membrane-permeant analog of the physiological PKC activator diacylglycerol. Staurosporine inhibited TEA transport with basal conditions, and after stimulation with the phorbolesters. The data provide the first evidence that PKC is involved in the regulation of the renal contraluminal transport system for organic cations.
Hohage
H
H
Department of Pharmacology and Toxicology, RWTH Aachen, FRG.
Mörth
D M
DM
Querl
I U
IU
Greven
J
J
D000818:Animals; D001692:Biological Transport; D004075:Diglycerides / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008297:Male; D011493:Protein Kinase C / Q000502:physiology*; D011817:Rabbits; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013757:Tetraethylammonium Compounds / Q000493:pharmacokinetics*
D004075:Diglycerides; D013757:Tetraethylammonium Compounds; C038237:1-oleoyl-2-acetylglycerol; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate