title: Effects of cannabinoid agonists on sheep sphincter of oddi in vitro.
abstract: OBJECTIVE
  According to recent studies, the endocannabinoid system plays an important role in both physiological and pathophysiological situations. The purpose of the present study was to investigate the effects of cannabinoid (CB) agonists on isolated sheep sphincter of Oddi (SO)in vitro.
  
  
  METHODS
  The isolated sheep SO tissues were mounted in organ baths and tested for isometric tension and cyclic GMP levels (cGMP) in response to the non-selective CB receptor agonist WIN 55,212-2 and the potent CB1 receptor agonist methanandamide in the presence and absence of the selective CB1 antagonist SR 141716A, the selective CB2 antagonist SR 144528 and the nonspecific inhibitor of nitric oxide (NO) synthase L-NAME.
  
  
  RESULTS
  CB agonists relaxed SO in a concentration-dependent manner. These relaxations did not reduce in the presence of SR 144528 but were significantly reduced by SR 141716A and L-NAME. Carbachol significantly increased the cGMP levels compared with the control group and both of the CB receptor agonists significantly increased the cGMP levels compared with the control and carbachol groups. On the other hand, L-NAME prevented the increase in cGMP levels caused by CB agonists.
  
  
  CONCLUSIONS
  These results show that the relaxation by the agonists may be through CB1 receptors. The decrease of CB relaxation responses by L-NAME, a nonspecific inhibitor of NO synthase, and the increase of cGMP levels in the SO tissues by CB agonists which decreased by L-NAME show that the relaxation effects of these agonists may also partially be via increasing the NO synthesis or release.
authors.affiliation: Departement of Pharmacology, University of Cumhuriyet, Sivas, Turkey. saracbulent@mynet.com
authors.forename: Bulent
authors.initials: B
authors.lastname: Sarac
authors.forename: Nedim
authors.initials: N
authors.lastname: Durmus
authors.forename: Ahmet
authors.initials: A
authors.lastname: Altun
authors.forename: Mustafa
authors.initials: M
authors.lastname: Turan
authors.forename: Tijen
authors.initials: T
authors.lastname: Kaya
authors.forename: Mehmet
authors.initials: M
authors.lastname: Sencan
authors.forename: Ihsan
authors.initials: I
authors.lastname: Bagcivan
mesh_terms: D000700:Analgesics / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D048588:Benzoxazines / Q000494:pharmacology; D001892:Camphanes / Q000494:pharmacology; D063386:Cannabinoid Receptor Agonists; D002186:Cannabinoids / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D009924:Organ Culture Techniques; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D000077285:Rimonabant; D012756:Sheep / Q000502:physiology*; D009803:Sphincter of Oddi / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000700:Analgesics; D001095:Arachidonic Acids; D048588:Benzoxazines; D001892:Camphanes; D063386:Cannabinoid Receptor Agonists; D002186:Cannabinoids; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; C110630:SR 144528; C088155:methanandamide; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D002217:Carbachol; D006152:Cyclic GMP; D000077285:Rimonabant; D019331:NG-Nitroarginine Methyl Ester