Investigation of relaxant effects of new agents affecting nitric oxide/cyclic guanosine monophosphate pathway on sheep oddi sphincter.
OBJECTIVE
Nitric oxide (NO) is a potent nonadrenergic, noncholinergic mediator of gastrointestinal smooth muscle. We aimed to investigate the effects of new NO/cyclic guanosine monophosphate (cGMP) pathway-affecting agents at the sheep sphincter of Oddi (SO) in vitro.


METHODS
Sheep SO rings were mounted in organ baths and tested for isometric tension and cGMP levels in response to 3,3-bis(aminoethyl)-1-hydroxy-2-oxo-1-triazene; 3-morpholinosydnonimine hydrochloride (SIN-1); and BAY 41-2272 in the presence and absence of 1H-(1,2,4)oxadiazole(4,3-a)quinoxalin-1-one (ODQ).


RESULTS
3,3-bis(Aminoethyl)-1-hydroxy-2-oxo-1-triazene; SIN-1; and BAY 41-2272 relaxed SO rings in a concentration-dependent manner. These relaxations were significantly decreased in the presence of ODQ (P < 0.05). All agents significantly increased the cGMP levels compared with the control group (P < 0.05). The increased cGMP levels in the 3,3-bis(aminoethyl)-1-hydroxy-2-oxo-1-triazene- and BAY 41-2272-treated groups were significantly different from both control and carbachol groups (P < 0.05), whereas the increase in the SIN-1 group was significantly different from all groups (P < 0.05). The cGMP levels were significantly lower in the presence of ODQ compared with its absence (P < 0.05).


CONCLUSIONS
The relaxation of SO rings by these agents may be via increasing the levels of cGMP. The additional increase produced by SIN-1 may be the combined effects of NO generation and activation of guanylyl cyclase.
Sarac
Bulent
B
Departments of Pharmacology, Cumhuriyet University School of Medicine, Sivas, Turkey. saracbulent@mynet.com
Durmus
Nedim
N
Bagcivan
Ihsan
I
Altun
Ahmet
A
Turan
Mustafa
M
Sencan
Mehmet
M
D000818:Animals; D002217:Carbachol / Q000008:administration & dosage; D006152:Cyclic GMP / Q000032:analysis / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006162:Guanylate Cyclase / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009126:Muscle Relaxation; D009130:Muscle, Smooth / Q000187:drug effects*; D009569:Nitric Oxide / Q000032:analysis / Q000378:metabolism*; D010069:Oxadiazoles / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology*; D012756:Sheep; D009803:Sphincter of Oddi / Q000187:drug effects* / Q000378:metabolism; D014226:Triazenes / Q000494:pharmacology*
C105351:1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene; C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; C423582:3-(4-Amino-5-cyclopropylpyrimidine-2-yl)-1-(2-fluorobenzyl)-1H-pyrazolo(3,4-b)pyridine; D010069:Oxadiazoles; D011720:Pyrazoles; D011725:Pyridines; D011810:Quinoxalines; D014226:Triazenes; D009569:Nitric Oxide; C002385:linsidomine; D002217:Carbachol; D008981:Molsidomine; D006162:Guanylate Cyclase; D006152:Cyclic GMP