Effect of protein kinase C inhibitors on the actions of phorbol esters on vascular tone and adrenergic transmission in the isolated rat kidney

Journal Article · Tue May 01 00:00:00 EDT 1990 · Journal of Pharmacology and Experimental Therapeutics; (USA)

OSTI ID:7011584

Sehic, E; Malik, K U ^[1]

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1. Univ. of Tennessee, Memphis (USA)

The effect of protein kinase C (PKC) inhibitors 1-(5-isoquinoline-sulfonyl)-2-methylpiperazine (H-7), polymyxin B (PMB), D-sphingosine (SPH), sangivamycin (SNG) and staurosporin (ST) on the action of PKC activators phorbol 12,13-dibutyrate (PDBu) and 12-o-tetradecanoylphorbol-13-acetate (TPA), on adrenergic neuroeffector events was investigated to determine the contribution of PKC in adrenergic transmission in the rat kidney. Infusion of TPA (5 x 10(-6) mM) or PDBu (6 x 10(-6) mM) produced renal vasoconstriction and enhanced the overflow of tritium elicited by periarterial renal nerve stimulation (RNS) (2 Hz) in the isolated rat kidney perfused with Tyrode's solution and prelabeled with (3H)norepinephrine. H-7 (2.7 x 10(-3) mM) and ST (2 x 10(-5) mM) did not alter RNS-induced overflow of tritium but attenuated the vasoconstrictor response to RNS and exogenous NE. PMB (1 x 10(-8) mM) and SPH (3.3 x 10(-4) mM) but not SNG (3.3 x 10(-3) mM) attenuated the RNS-induced overflow of tritium but increased the basal renal vascular tone and enhanced the vasoconstrictor response to RNS and exogenous NE. H-7, PMB, SPH, SNG or ST failed to alter the effects of PDBu to increase basal vascular tone and the overflow of tritium and the increase in renal vasoconstriction to RNS. PMB at 1 x 10(-9) mM but not at 1 x 10(-8) mM and SPH (3.3 x 10(-4) mM) but not H-7, SNG or ST inhibited the effect of TPA to increase the overflow of tritium. The effect of TPA on the vasoconstrictor response to RNS or to increase basal vascular tone was not altered by PKC inhibitors. These data suggest that in the rat kidney, PKC is either resistant to the actions of H-7, PMB, SPH, SNG and ST, or PDBu and TPA produce renal vasoconstriction and facilitate adrenergic transmission by a mechanism unrelated to PKC activation.

• OSTI ID: 7011584
• Journal Information: Journal of Pharmacology and Experimental Therapeutics; (USA), Vol. 253:2; ISSN 0022-3565
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
59 BASIC BIOLOGICAL SCIENCES
ENZYME INHIBITORS
BIOCHEMICAL REACTION KINETICS
KIDNEYS
VASOCONSTRICTION
PHORBOL ESTERS
BIOLOGICAL EFFECTS
NERVES
NORADRENALINE
PERFUSED ORGANS
RATS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ADRENAL HORMONES
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BODY
CARCINOGENS
CARDIOTONICS
CARDIOVASCULAR AGENTS
DRUGS
ESTERS
HYDROGEN COMPOUNDS
ISOTOPE APPLICATIONS
KINETICS
MAMMALS
NERVOUS SYSTEM
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANS
REACTION KINETICS
RODENTS
SYMPATHOMIMETICS
VERTEBRATES
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