Background/Aims: Nitric oxide (NO) is a major inhibitor in various parts of the gastrointestinal tract. This study was designed to compare the effects of YC-1, NO-independent soluble guanylate cyclase (sGC) activator, and DEA/NO, NO-nucleophile adduct, on sheep sphincters of Oddi (SO). Methods: SO rings were mounted in a tissue bath and tested for changes in isometric tension in response to 3-(5'-hydroxymethyl- 2'-furyl)-1-benzylindazole (YC-1, 10(-10)-10(-5) M), diethylamine/NO complex (DEA/NO, 10(-8)-10(-4) M). We also evaluated the effect of YC-1 (10(-6) and 10(-5) M) and DEA/NO (10(-5) and 10(-4) M) on the levels cyclic GMP (cGMP) in isolated SO. Results: YC-1 (10(-10)-10(-5) M) and DEA/NO (10(-8)-10(-4) M) induced concentration-dependent relaxation of isolated SO rings precontracted with carbachol (10(-6) M). The pEC(50) value of DEA/NO was significantly lower than those for YC-1 (p < 0.05), with no change of E-max values. YC-1 increased cGMP levels more than control, carbachol and DEA/NO groups (p < 0.05). Conclusion: These results show that YC-1 is a more potent relaxant than DEA/NO and causes more elevation of cGMP levels in isolated SO rings. Copyright (C) 2006 S. Karger AG, Basel and IAP.