title: Pretreatment with clonidine caused desensitization to WIN 55,212-2 in guinea pig ileum.
abstract: Considering the existence of cross-tolerance between clonidine and morphine besides the same interaction between morphine and WIN 55,212-2 persuaded us to verify this fact between WIN 55,212-2 and clonidine in guinea pig ileum, which is a well-known model to examine the mode of action of cannabinoids and α2 -adenoceptor agonists The rectangular pulses were passed to the 0.5 g stretched ileum segments that were fixed in 20-ml organ bath. PowerLab system and Graphpad Prism were applied to record twitches and analyse the data. Electrically evoked contractions were dose-dependently inhibited by WIN 55,212-2 and clonidine (pD2 = 8.56 ± 0.41 and 7.65 ± 0.15, respectively). Tolerance to this effect could be induced by 4-h incubation with WIN 55,212-2 (3 × IC50 ) (pD2  = 6.36 ± 0.26, degree of tolerance: 159.32) (P < 0.01) but not with clonidine (2 × IC50 and 4 × IC50 ) for different time courses. Dose-response curve for inhibitory action of WIN 55,212-2 was shifted to the right after 4-h incubation with clonidine (3 × 10(-10) m) comparing to the untreated tissues (pD2  = 5.26 ± 0.69, degree of tolerance: 2000) (P < 0.001). This observation provides the evidence for the cannabinoid-noradrenergic systems interaction in the enteric nervous system as a simplified representative for central nervous system.
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, 13145-784, Iran.
authors.forename: F
authors.initials: F
authors.lastname: Rezania
authors.forename: L
authors.initials: L
authors.lastname: Mohaghegh Shalmani
authors.forename: R
authors.initials: R
authors.lastname: Rahimian
authors.forename: A R
authors.initials: AR
authors.lastname: Dehpour
authors.forename: S
authors.initials: S
authors.lastname: Ejtemaei Mehr
mesh_terms: D000818:Animals; D048588:Benzoxazines / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D003000:Clonidine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D004558:Electric Stimulation; D017615:Enteric Nervous System / Q000187:drug effects* / Q000502:physiology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009025:Morpholines / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009281:Naphthalenes / Q000037:antagonists & inhibitors* / Q000494:pharmacology*
chemical_list: D048588:Benzoxazines; D009025:Morpholines; D009281:Naphthalenes; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D003000:Clonidine
keywords: WIN 55,212-2; cannabinoid; clonidine; guinea pig ileum