Dual actions of dephostatin on the nitric oxide/cGMP-signalling pathway in porcine iliac arteries
2005 (English)In: European Journal of Pharmacology, ISSN 0014-2999, E-ISSN 1879-0712, Vol. 521, no 1-3, 124-132 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2005. Vol. 521, no 1-3, 124-132 p.
Dephostatin, GEA 3175, Nitric oxide, Protein phosphorylation, Relaxation, SNAP
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-30909DOI: 10.1016/j.ejphar.2005.08.023Local ID: 16577OAI: oai:DiVA.org:liu-30909DiVA: diva2:251732