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

E. Sehic, Kafait Malik

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3 Citations (Scopus)

Abstract

The effect of protein kinase C (PKC) inhibitors 1-(5-isoquinolinesulfonyl)-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.

Original languageEnglish (US)
Pages (from-to)497-507
Number of pages11
JournalJournal of Pharmacology and Experimental Therapeutics
Volume253
Issue number2
StatePublished - 1990

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Protein C Inhibitor
Phorbol Esters
Protein Kinase Inhibitors
Adrenergic Agents
Protein Kinase C
Blood Vessels
sangivamycin
Kidney
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
Sphingosine
Tritium
Phorbol 12,13-Dibutyrate
Tetradecanoylphorbol Acetate
Polymyxin B
Vasoconstrictor Agents
Vasoconstriction
Norepinephrine

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

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title = "Effect of protein kinase C inhibitors on the actions of phorbol esters on vascular tone and adrenergic transmission in the isolated rat kidney",
abstract = "The effect of protein kinase C (PKC) inhibitors 1-(5-isoquinolinesulfonyl)-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.",
author = "E. Sehic and Kafait Malik",
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T1 - Effect of protein kinase C inhibitors on the actions of phorbol esters on vascular tone and adrenergic transmission in the isolated rat kidney

AU - Sehic, E.

AU - Malik, Kafait

PY - 1990

Y1 - 1990

N2 - The effect of protein kinase C (PKC) inhibitors 1-(5-isoquinolinesulfonyl)-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.

AB - The effect of protein kinase C (PKC) inhibitors 1-(5-isoquinolinesulfonyl)-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.

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