Effects of nitroprusside, glyceryl trinitrate, and 8-bromo cyclic GMP on phosphorylase a formation and myosin light chain phosphorylation in rat aorta.
The effects of nitroprusside (NP), glyceryl trinitrate (GTN), and the 8-bromo analog of cyclic GMP (8-Br-cGMP) on norepinephrine (NE)-stimulated phosphorylase a formation and myosin light chain (MLC) phosphorylation were examined in the rat aorta. NE produced a time-dependent increase in tension, phosphorylase a formation, and MLC phosphorylation. The formation of phosphorylase a and phosphorylation of MLC were transient, since both processes declined to basal levels within 30 min after the addition of NE even though tension remained elevated. NP and GTN inhibited tension, phosphorylase a formation, and MLC phosphorylation although inhibition of phosphorylase was greater when strips were treated with submaximal (i.e., 0.01 microM) NE concentrations. GTN was a more effective inhibitor of phosphorylase a formation than NP in NE-treated strips, although both agents and 8-Br-cGMP inhibited MLC phosphorylation. The guanylate cyclase inhibitor methylene blue (10 microM) effectively prevented the effects of NP and GTN. The results suggest that NP, GTN, and 8-Br-cGMP inhibit phosphorylase kinase and MLC kinase activation by lowering Ca2+ in the cell. This hypothesis is supported by the observations that 8-Br-cGMP inhibited the Ca2+-dependent, KCl-induced phosphorylase a formation most markedly at reduced concentrations of extra-cellular Ca2+. In addition, neither NP, GTN, nor 8-Br-cGMP inhibited phosphorylase a formation in forskolin-treated tissues, which occurred in response to cAMP-dependent phosphorylation of phosphorylase b kinase.
Johnson
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Lincoln
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D000818:Animals; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D005292:Ferricyanides / Q000494:pharmacology*; D008751:Methylene Blue / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009218:Myosins / Q000378:metabolism*; D005996:Nitroglycerin / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D010762:Phosphorylase a / Q000096:biosynthesis*; D006005:Phosphorylases / Q000096:biosynthesis*; D010766:Phosphorylation; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats
D005292:Ferricyanides; D009599:Nitroprusside; C016276:8-bromocyclic GMP; D011189:Potassium Chloride; D010762:Phosphorylase a; D006005:Phosphorylases; D009218:Myosins; D005996:Nitroglycerin; D006152:Cyclic GMP; D008751:Methylene Blue; D009638:Norepinephrine