Influence of protein kinase C activators on vascular tone and adrenergic neuroeffector events in the isolated rat kidney.
To investigate if protein kinase C (PKC) activation is involved in mediating or modulating adrenergic transmission, we have investigated the effect of phorbol esters, PKC activators, on the release of adrenergic transmitter elicited by periarterial renal nerve stimulation (RNS) in the isolated rat kidney perfused with Tyrode's solution and prelabeled with [3H]norepinephrine. Infusion of 12-o-tetra-decanoyl-phorbol 13-acetate (TPA) at 5 x 10(-7) mM produced renal vasoconstriction and a rise in basal perfusion pressure without any consistent effect on the rise in tritium efflux or the perfusion pressure elicited by RNS. Higher concentrations of TPA (5 x 10(-6) to 5 x 10(-5) mM) increased both the basal as well as RNS-induced efflux of tritium; the basal perfusion pressure was increased so dramatically that the effect of RNS to raise perfusion pressure was reduced compared to that observed in the vehicle group. Infusion of phorbol-12,13-dibutyrate at 6 x 10(-6) mM reduced the basal but increased the RNS-induced efflux of tritium; the basal as well as the rise in perfusion pressure caused by RNS was increased. Phorbol-13-monoacetate that does not activate PKC failed to alter the basal or the increase in tritium efflux and perfusion pressure elicited by RNS. The rise in perfusion pressure produced by TPA or phorbol-12,13-dibutyrate was reduced by nifedipine (1.4 x 10(-6) mM) but it was abolished by omission of Ca++ from the perfusion medium. These data suggest that PKC activation with phorbol esters produces renal vasoconstriction by promoting influx of extracellular Ca++.(ABSTRACT TRUNCATED AT 250 WORDS)
Sehic
E
E
Department of Pharmacology, College of Medicine, University of Tennessee, Memphis.
Malik
K U
KU
D000818:Animals; D002118:Calcium / Q000378:metabolism; D004789:Enzyme Activation; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism* / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D009543:Nifedipine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D009638:Norepinephrine