Comparison of the effects of YC-1, DEA/NO, sodium nitroprusside and theophylline on the sheep sphincter of Oddi

Abstract

Objective: It has been demonstrated that nitric oxide (NO) plays an important physiological role in various parts of the gastrointestinal (GI) tract. This study was designed to show the existence of NO system in the sheep sphincters of Oddi (SO) and to compare the effects of drugs that affect NO system by different mechanisms. Material and Methods: SO rings were mounted in tissue baths with modified Krebs-Henseleit solution and aerated with 95% oxygen and 5% carbon dioxide. Electrical field stimulation (EFS) responses and concentration-response curves for 3-(5?-hydroxymethyl-2?-furyl)-1- benzyl indazole (YC-1, 10-10-10-5 M), diethylamine/NO complex (DEA/NO, 10-8-10-4 M), sodium nitroprusside (SNP, 10-8-3 × 10-4 M) and theophylline (10 -8-10-4 M) on SO rings precontracted with carbachol (10-6 M) were recorded isometrically with a Grass polygraph. 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 rings. Results: EFS-induced contractile responses was decreased by atropine (10-6 M) and guanethidine (10-5 M), but potentiated by L-NAME (3 × 10-5 M). YC-1 (10 -10-10-5 M), DEA/NO (10-8-10-4 M), SNP (10-8-3 × 10-4 M) and theophylline (10 -8-10-4 M) induced concentration-dependent relaxation of isolated SO rings precontracted with carbachol (10-6 M). In carbacholprecontracted SO rings the order of potency was YC-1>DEA/NO>SNP= theophylline. YC-1 and DEA/NO increased cGMP levels more than control and carbachol groups (p> 0.05). Conclusion: These results show that NO system exists in the sheep SO. YC-1, DEA/NO, SNP and theophylline induce quantitatively different relaxation of SO rings. YC-1 is a more potent relaxant than other drugs and causes more elevation of cGMP levels in isolated SO rings. Copyright © 2005 by Türkiye Klinikleri.