Comparative relaxant effects of YC-1 and DEA/NO on the sheep sphincter of Oddi

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-benzyl indazole (YC-1, 10−10-10−5M), diethylamine/NO complex (DEA/NO, 10−8-10−4M). We also evaluated the effect of YC-1 (10−6 and 10−5M) and DEA/NO (10−5 and 10−4M) on the levels cyclic GMP (cGMP) in isolated SO. Results: YC-1 (10−10-10−5 M) and DEA/NO (10−8-10−4M) induced concentration-dependent relaxation of isolated SO rings precontracted with carbachol (10−6M). The pEC50 value of DEA/NO was significantly lower than those for YC-1 (p < 0.05), with no change of Emax 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.