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


CONCLUSIONS
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.
Department of Pharmacology, Cumhuriyet University School of Medicine, Sivas, Turkey. ibagcivan@cumhuriyet.edu.tr
Ihsan
I
Bagcivan
Tijen
T
Kaya
Mustafa
M
Turan
Baris
B
Karadas
Bülent
B
Sarac
Mustafa
M
Duman
D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism; D006834:Hydrazines / Q000494:pharmacology*; D066298:In Vitro Techniques; D007191:Indazoles / Q000494:pharmacology*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology; D009589:Nitrogen Oxides / Q000494:pharmacology*; D012756:Sheep; D009803:Sphincter of Oddi / Q000187:drug effects* / Q000378:metabolism
D006834:Hydrazines; D007191:Indazoles; D009466:Neuromuscular Blocking Agents; D009589:Nitrogen Oxides; C090937:3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole; C084012:1,1-diethyl-2-hydroxy-2-nitrosohydrazine; D006152:Cyclic GMP