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

Pancreatology. 2006;6(3):215-9. doi: 10.1159/000091959. Epub 2006 Mar 9.

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(-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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Cyclic GMP / metabolism
  • Hydrazines / pharmacology*
  • In Vitro Techniques
  • Indazoles / pharmacology*
  • Male
  • Muscle Relaxation / drug effects*
  • Neuromuscular Blocking Agents / pharmacology
  • Nitrogen Oxides / pharmacology*
  • Sheep
  • Sphincter of Oddi / drug effects*
  • Sphincter of Oddi / metabolism

Substances

  • Hydrazines
  • Indazoles
  • Neuromuscular Blocking Agents
  • Nitrogen Oxides
  • 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole
  • 1,1-diethyl-2-hydroxy-2-nitrosohydrazine
  • Cyclic GMP