Inhibition of purified (Na+,K+)-ATPase activity from porcine cerebral cortex by NO generating drugs.
We tested the effects of several nitric oxide (NO) generating compounds on the activity of sodium-potassium adenosine 5'-triphosphatase [(Na+,K+)-ATPase] purified from porcine cerebral cortex. Sodium nitroprusside (SNP), S-nitroso-N-acetylpenicillamine (SNAP), 3-morpholinosydnonimine (SIN-1) and (d1)-(E)-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexeneamide (NOR 3) inhibited the (Na+,K+)-ATPase activity dose dependently. Superoxide dismutase, a NO scavenger, and sulfhydryl (SH) compounds, reduced-form glutathione (rGSH) and dithiothreitol (DTT), prevented the inhibitory action of SNAP, SIN-1 and NOR 3 but not of SNP, when applied simultaneously with NO generating compounds, and this enzyme inhibition could be reactivated by the incubation with these SH compounds but not with SOD. The inhibitory action by SNP was magnified by simultaneous application of DTT. These results suggest that NO generating compounds, SNAP, SIN-1 and NOR 3 but not SNP, may release NO or NO-derived products and may inhibit (Na+,K+)-ATPase activity by interacting with a SH group at the active site of the enzyme.
Sato
T
T
Department of Pharmacology, Kagoshima University Dental School, Japan.
Kamata
Y
Y
Irifune
M
M
Nishikawa
T
T
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000201:enzymology; D004229:Dithiothreitol / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008981:Molsidomine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D009574:Nitro Compounds / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D026423:S-Nitroso-N-Acetylpenicillamine; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000302:isolation & purification; D013439:Sulfhydryl Reagents / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D013552:Swine
D004791:Enzyme Inhibitors; D009574:Nitro Compounds; D013439:Sulfhydryl Reagents; D009599:Nitroprusside; D009569:Nitric Oxide; C002385:linsidomine; D026423:S-Nitroso-N-Acetylpenicillamine; C061872:FK 409; D008981:Molsidomine; D013482:Superoxide Dismutase; D000254:Sodium-Potassium-Exchanging ATPase; D010396:Penicillamine; D004229:Dithiothreitol