The relaxant activity of 4,7-dimethyl-1,2,5-oxadiazolo[3,4-d]-pyridazine 1,5,6-trioxide in the mouse corpus cavernosum


Gocmen C. , Buyuknacar H. S. , Kots A., Murad F., Kiroglu O. , Kumcu E.

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, vol.316, no.2, pp.753-761, 2006 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 316 Issue: 2
  • Publication Date: 2006
  • Doi Number: 10.1124/jpet.105.094250
  • Title of Journal : JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
  • Page Numbers: pp.753-761

Abstract

We have studied the effect of an activator of soluble guanylate cyclase 4,7-dimethyl-1,2,5-oxadiazolo[3,4-d] pyridazine 1,5,6-trioxide ( FPTO) on the tone and nitrergic relaxation responses of mouse cavernous strips and compared FPTO to a known nitric oxide donor sodium nitroprusside. FPTO thiol-dependently generated nitric oxide measured by polarography and activated purified human soluble guanylate cyclase. FPTO and sodium nitroprusside relaxed the cavernous tissue in a concentration-dependent manner. A nitric-oxide synthase inhibitor N(omega)-nitro- L-arginine did not alter the relaxations to FPTO or sodium nitroprusside, whereas soluble guanylate cyclase inhibitor 1H-[ 1,2,4] oxadiazolo[ 4,3-a] quinoxalin-1-one (ODQ) suppressed relaxation to FPTO and sodium nitroprusside. Exogenously added thiols L-cysteine or dithiothreitol inhibited the relaxant responses to FPTO but not to sodium nitroprusside, whereas glutathione did not influence the responses to both agents.