Myosin light chain phosphorylation in contraction and relaxation of intact rat thoracic aorta.
Myosin light chain phosphorylation in intact rat thoracic aorta was elevated during contraction induced by 0.3 microM norepinephrine, but was not maintained. Addition of 0.5 microM sodium nitroprusside to norepinephrine treated rat aorta strips led to elevation of cyclic GMP levels, relaxation of tension, and dephosphorylation of myosin light chain. Depletion of extracellular calcium or addition of calmodulin antagonists trifluoperazine and W7 diminished the contraction and phosphorylation of myosin light chain by norepinephrine, but did not prevent dephosphorylation by sodium nitroprusside or the elevated levels of cyclic GMP. Isoproterenol, 8-bromo cyclic GMP, and dibutyryl cyclic AMP all caused dephosphorylation of myosin light chain and induced relaxation during the period of development of tone. Eight other proteins had increased phosphorylation following norepinephrine treatment and one protein had less phosphorylation. The different proteins phosphorylated by norepinephrine showed varying degrees of sensitivity to Ca2+-free solution and to the calmodulin antagonists. The pattern of protein phosphorylation caused by sodium nitroprusside was best mimicked by 8-bromo cyclic GMP, rather than isoproterenol and dibutyryl cyclic AMP. These proteins were, generally, unaffected by Ca2+-free solution and the calmodulin antagonists. The present observations support the hypothesis that vasodilators inhibit tone development through myosin light chain dephosphorylation. Furthermore, the nitrovasodilators act through elevation of cyclic GMP and phosphorylation of proteins by cyclic GMP-dependent protein kinase.
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009218:Myosins / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010766:Phosphorylation; D051381:Rats; D011919:Rats, Inbred Strains; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D009599:Nitroprusside; D009218:Myosins; D006152:Cyclic GMP; D002118:Calcium; D009638:Norepinephrine