Masashi Nakagawa1,2, Tadayoshi Takeuchi1, Satomi
Niioka1, Michiru Yamaji1,
Yutaka Okishio1, Hideaki Nishio1 and Fumiaki Hata1,3,*
1Department╩of Veterinary Pharmacology, College of Agriculture and 3Department of Molecular Physiology and Biochemistry,
Research Institute for Advanced Science and Technology, Osaka Prefecture University, Sakai 599-8531, Japan
2Department╩of Anesthesiology, Sakai Municipal Hospital, Sakai 590-0064, Japan
*╩To whom correspondence should be addressed(1).
Abstract: Participation of the nitric oxide-cyclic GMP pathway in nonadrenergic, noncholinergic (NANC) relaxation induced by electrical field stimulation of longitudinal muscle of the rectum of Wistar-ST rats was studied by using a selective inhibitor of soluble guanylyl cyclase, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). ODQ concentration dependently inhibited the relaxation and at 10╩mM, maximally inhibited it by 83%. However, results obtained with NG-nitro-L-arginine, L-arginine and exogenously added nitric oxide excluded the participation of nitric oxide in the relaxation. An inhibitor of cyclic GMP-dependent protein kinase (PKG) partially (39%) inhibited the relaxation. ODQ also significantly inhibited the relaxation, which persisted after the PKG inhibitor-treatment, by 85%. The results strongly suggest that ODQ inhibits the NANC relaxation in a cyclic GMP-PKG pathway-independent manner.
Keywords: 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), Soluble guanylyl cyclase,
Nonadrenergic, noncholinergic (NANC) relaxation