Cyclic GMP accumulation in normal and diabetic primary culture adult rat ventricular cardiomyocytes: a minor role for nitric oxide in phosphorylase activation.
The potential role of nitric oxide in the diabetes-induced hypersensitive activation of glycogen phosphorylase by epinephrine was investigated in adult rat ventricular cardiomyocytes. Pretreatment of normal and diabetic-derived cells with 1 mM sodium nitroprusside significantly diminished the phosphorylase activation response by nearly 20% in both normal and diabetic myocytes but failed to alter the hypersensitivity of the diabetic cells. Nitroprusside increased cGMP levels in both normal and diabetic myocytes although the effect was more pronounced in the diabetic cells. Epinephrine did not alter cellular cGMP content and cGMP levels were consistently lower in diabetic myocytes when compared with normal myocytes. Preincubation of ventricular myocytes with the nitric oxide synthase inhibitor L-iminoethyl ornithine did not affect phosphorylase activation. These data indicate that nitric oxide plays a minor role in phosphorylase activation by epinephrine in rat cardiomyocytes and suggest that signal transduction via nitric oxide is not affected by the onset of diabetes.
Buczek-Thomas
J A
JA
Department of Biochemistry and Molecular Biology, University of Massachusetts Medical School, Worcester 01655, USA.
Miller
T B
TB
D000818:Animals; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000096:biosynthesis*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D006352:Heart Ventricles; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D009952:Ornithine / Q000031:analogs & derivatives / Q000494:pharmacology; D006005:Phosphorylases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
D004791:Enzyme Inhibitors; D009599:Nitroprusside; D009569:Nitric Oxide; C065027:N(G)-iminoethylornithine; D009952:Ornithine; D019001:Nitric Oxide Synthase; D006005:Phosphorylases; D006152:Cyclic GMP; D004837:Epinephrine