1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) inhibits cyclic GMP-PKG pathway-independent nonadrenergic, noncholinergic relaxation in longitudinal muscle of the rectum of Wistar-ST rats.
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 microM, maximally inhibited it by 83%. However, results obtained with N(G)-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.
Nakagawa
M
M
Department of Veterinary Pharmacology, College of Agriculture, Research Institute for Advanced Science and Technology, Osaka Prefecture University, Sakai, Japan.
Takeuchi
T
T
Niioka
S
S
Yamaji
M
M
Okishio
Y
Y
Nishio
H
H
Hata
F
F
D000818:Animals; D006152:Cyclic GMP / Q000502:physiology*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors*; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009479:Neuropeptides / Q000494:pharmacology; D019335:Nitroarginine / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012007:Rectum / Q000187:drug effects* / Q000502:physiology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D004791:Enzyme Inhibitors; D009479:Neuropeptides; D010069:Oxadiazoles; D010446:Peptide Fragments; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011810:Quinoxalines; C075647:pituitary adenylate-cyclase-activating-peptide (6-38); D019335:Nitroarginine; D014660:Vasoactive Intestinal Peptide; C047945:vasoactive intestinal peptide (10-28); D017869:Cyclic GMP-Dependent Protein Kinases; D006162:Guanylate Cyclase; D006152:Cyclic GMP