Activation of a cytosolic ADP-ribosyltransferase by nitric oxide-generating agents.
Sodium nitroprusside is a vasodilator and an inhibitor of platelet activation. It is thought that these effects are mediated by the spontaneous release of nitric oxide and stimulation of cytosolic guanylate cyclase. We have found that sodium nitroprusside (5-200 microM) greatly increased a cytosolic ADP-ribosyltransferase that ADP-ribosylates a soluble 39-kDa protein. This activity causes the mono-ADP-ribosylation of the 39-kDa protein, since digestion with snake venom phosphodiesterase releases 5'-AMP. This enzyme is present in platelets, brain, heart, intestine, liver, and lung. The effect of sodium nitroprusside is not related to stimulation of soluble guanylate cyclase and the production of cyclic GMP because cyclic GMP, dibutyryl cyclic GMP, and 8-bromo-cyclic GMP are ineffective. 3-Morpholinosydnonimine (commonly known as SIN-1) (20-1000 micrograms/ml), another compound that acts through the spontaneous formation of nitric oxide as does sodium nitroprusside, also stimulates ADP-ribosylation of the 39-kDa protein. Hemoglobin, which binds nitric oxide, inhibits sodium nitroprusside's activation of the cytosolic ADP-ribosyltransferase. These studies demonstrate a novel action of nitric oxide related to the activation of an endogenous ADP-ribosyltransferase. The physiological role of this ADP-ribosylation needs further exploration.
Brüne
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Division of Cell Biology, Burroughs Wellcome Co., Research Triangle Park, North Carolina 27709.
Lapetina
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D036002:ADP Ribose Transferases; D000818:Animals; D001792:Blood Platelets / Q000201:enzymology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000097:blood / Q000494:pharmacology; D003600:Cytosol / Q000201:enzymology; D004789:Enzyme Activation; D006801:Humans; D019811:Hydroxylamine; D006898:Hydroxylamines / Q000494:pharmacology; D007700:Kinetics; D009569:Nitric Oxide / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D009928:Organ Specificity; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D051381:Rats
D006898:Hydroxylamines; D009599:Nitroprusside; D019811:Hydroxylamine; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D036002:ADP Ribose Transferases; D011065:Poly(ADP-ribose) Polymerases; D006152:Cyclic GMP