Abstract

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<sup>–10</sup>–10<sup>–5</sup>M), diethylamine/NO complex (DEA/NO, 10<sup>–8</sup>–10<sup>–4</sup>M). We also evaluated the effect of YC-1 (10<sup>–6</sup> and 10<sup>–5</sup>M) and DEA/NO (10<sup>–5</sup> and 10<sup>–4</sup>M) on the levels cyclic GMP (cGMP) in isolated SO. Results: YC-1 (10<sup>–10</sup>–10<sup>–5</sup> M) and DEA/NO (10<sup>–8</sup>–10<sup>–4</sup>M) induced concentration-dependent relaxation of isolated SO rings precontracted with carbachol (10<sup>–6</sup>M). The pEC<sub>50</sub> value of DEA/NO was significantly lower than those for YC-1 (p < 0.05), with no change of E<sub>max</sub> 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.

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