s-nitro-n-acetylpenicillamine and dephostatin

We examined the effects of the nitrosoamine dephostatin on the nitric oxide (NO)/cyclic guanosine 3',5'-monophosphate (cGMP)-signalling in porcine iliac arteries. Dephostatin has been characterised as a tyrosine phosphatase inhibitor, but Western blot analyses showed that dephostatin did not augment tyrosine phosphorylation of arterial proteins. However, dephostatin relaxed pre-contracted arteries, and this effect was antagonised by the soluble guanylyl cyclase inhibitor 1H[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). Furthermore, dephostatin increased the cGMP content and the serine phosphorylation of vasodilator-stimulated phosphoprotein. Dephostatin also inhibited the relaxation induced by acetylcholine and the NO-donor S-nitroso-N-acetyl-penicillamine (SNAP). In contrast, dephostatin did not affect the NO-dependent actions of 1,2,3,4-Oxatriazolium, 3-(3-chloro-2-metylphenyl)-5-[[(4methylphenyl)sulfonyl]amino]-hydroxide inner salt (GEA 3175). Measurement of NO revealed that dephostatin accelerated the consumption of NO. In conclusion, dephostatin exerts dual effects on the NO/cGMP-signalling pathway in iliac arteries. The drug actions included scavenging of NO, but also stimulation of cGMP production. These effects were not related to inhibition of tyrosine phosphatases.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Acetylcholine; Animals; Blotting, Western; Cyclic GMP; Enzyme Inhibitors; Guanylate Cyclase; Hydroquinones; Iliac Artery; In Vitro Techniques; Nitric Oxide; Nitric Oxide Donors; Oxadiazoles; Penicillamine; Phenylephrine; Phosphoproteins; Phosphorylation; Protein Tyrosine Phosphatases; Quinoxalines; Serine; Signal Transduction; Swine; Triazoles; Tyrosine; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents