Diacylglycerol and protein kinase mediated noradrenergic responses in perfused rat kidneys.
The role of protein kinases in renal noradrenergic stimulation was examined using sphingosine, 1-(5-isoquinolinylsulfonyl)-2-methyl-piperizine (H7), using sphingosine, 1-(5-isoquinolinylsulfonyl)-2-methyl-piperizine (H7), or staurosporine to inhibit the responses to norepinephrine (NE, 60 nM) in isolated perfused rat kidneys. Sphingosine (20 mumol/L) increased the noradrenergic vasoconstrictor response. H7 (10 mumol/L) partially blocked the immediate vasoconstrictor response and completely inhibited it after 2 min without altering the antinatriuretic and antilithuretic responses. H7 also blocked the increase in free water produced by NE, which is consistent with the inhibition of protein kinase A linked to beta-adrenergic stimulation. Staurosporine (10 nmol/L) partially inhibited noradrenergic vasoconstriction and antinatriuresis, and it completely blocked the depression of gluconeogenic responses to NE in pyruvate-perfused kidneys. To examine the role of diacylglycerol and protein kinase C in the renal responses to NE, we used oleoyl-acetyl-glycerol (OAG, 50-100 microM) or phorbol-12-myristyl-13-acetate (TPA, 5-50 nM). TPA slowly vasoconstricted the kidney and reduced GFR and fractional Na+, Li+, and free water excretion. Amiloride (1 mM) prevented the TPA responses. OAG mimicked the effects of TPA except that vasoconstriction occurred more rapidly and was brief. Both TPA and OAG acted like alpha 1-adrenergic agonists. These results indicate that diaclyglycerol and protein kinase are involved in the prolonged effects of NE on vasoconstriction. GFR, and proximal tubular reabsorption.
Baines
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Department of Clinical Biochemistry, Banting Institute, University of Toronto, Ont., Canada.
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D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D004075:Diglycerides / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005943:Gluconeogenesis / Q000187:drug effects; D005989:Glycerides / Q000494:pharmacology*; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000294:innervation*; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology / Q000502:physiology*; D010477:Perfusion; D010879:Piperazines / Q000494:pharmacology; D011494:Protein Kinases / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects; D013110:Sphingosine / Q000494:pharmacology; D019311:Staurosporine; D013564:Sympathetic Nervous System / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects
D000470:Alkaloids; D004075:Diglycerides; D005989:Glycerides; D007546:Isoquinolines; D010879:Piperazines; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011494:Protein Kinases; D019311:Staurosporine; D013110:Sphingosine; D013755:Tetradecanoylphorbol Acetate; D009638:Norepinephrine