Altered responsiveness of guanylyl cyclase to nitric oxide following treatment of cardiomyocytes with S-nitroso-D,L-acetylpenicillamine and sodium nitroprusside.
The stimulation of cardiomyocyte guanylyl cyclase by nitric oxide (NO)-donor drugs was examined before and after exposure of these cells to the NO-donor drugs: S-nitroso-d,l-acetylpenicillamine (SNAP) and sodium nitroprusside (SNP). Short- (2-hr) and long-term (24-hr) exposure attenuated the maximal stimulation of GC by either SNAP or SNP by up to 80% ("desensitization"). However this "desensitization" of the myocardial GC was atypical in nature in that the reduction in maximal NO-stimulated GC activity was associated with an increase in the affinity of the GC towards either NO-donor, a finding not as yet reported. There was also evidence of "cross-desensitization" of GC (e.g., SNAP exposure decreasing the stimulatory effect of SNP). Further, this is the first time that SNAP-induced desensitization of GC has been observed.
Davis
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JP
College of Medicine, University of Saskatchewan, 107 Wiggins Road, Saskatoon, Saskatchewan, S7N-5E, Canada.
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Sulakhe
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D000818:Animals; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D006162:Guanylate Cyclase / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology*; D009599:Nitroprusside / Q000378:metabolism / Q000494:pharmacology*; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D026423:S-Nitroso-N-Acetylpenicillamine
D004791:Enzyme Inhibitors; D009599:Nitroprusside; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D006162:Guanylate Cyclase; D010396:Penicillamine