title: Attenuation of serotonin-induced itch responses by inhibition of endocannabinoid degradative enzymes, fatty acid amide hydrolase and monoacylglycerol lipase.
abstract: Itch and pain are two irritating sensations sharing a lot in common. Considering the antinociceptive effects of blockade of endocannabinoid degrading enzymes in pain states, we attempted to reduce scratching behavior by endocannabinoid modulation, i.e. by inhibiting fatty acid amide hydrolase (FAAH), monoacylglycerol lipase (MAGL), or cellular uptake of endocannabinoids. Scratching behavior was induced by intradermal injection of serotonin to Balb/c mice. URB597 (10 mg/kg, i.p.), a FAAH inhibitor, JZL184 (16 mg/kg, i.p.), a MAGL inhibitor, and AM404 (10 mg/kg, i.p.), an endocannabinoid transport inhibitor, were given to evaluate the effects of endocannabinoid modulation on scratching responses. Then, the CB1 receptor antagonist, AM251 (1 mg/kg, i.p.), and the CB2 receptor antagonist, SR144528 (1 mg/kg, i.p.), were administered to determine whether cannabinoid receptors mediate these effects. URB597 and JZL184, but not AM404, attenuated serotonin-induced scratches. The inhibitory effect of URB597 was reversed by SR144528, but cannabinoid receptor antagonists had no other effects on modulation by the inhibitors. We propose that augmenting the endocannabinoid tonus by inhibition of degradative enzymes, FAAH and MAGL, but not cellular uptake, may be a novel target for the development of antipruritic agents.
authors.affiliation: Department of Medical Pharmacology, Faculty of Medicine, Trakya University, 22030, Edirne, Turkey.
authors.forename: Nurcan Calimli
authors.initials: NC
authors.lastname: Tosun
authors.forename: Ozgur
authors.initials: O
authors.lastname: Gunduz
authors.forename: Ahmet
authors.initials: A
authors.lastname: Ulugol
mesh_terms: D000581:Amidohydrolases / Q000378:metabolism*; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D001549:Benzamides / Q000627:therapeutic use; D052117:Benzodioxoles / Q000627:therapeutic use; D001892:Camphanes / Q000627:therapeutic use; D002219:Carbamates / Q000627:therapeutic use; D063388:Endocannabinoids / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008994:Monoacylglycerol Lipases / Q000378:metabolism*; D010880:Piperidines / Q000627:therapeutic use; D011537:Pruritus / Q000139:chemically induced / Q000188:drug therapy / Q000201:enzymology*; D011720:Pyrazoles / Q000627:therapeutic use; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors; D043885:Receptor, Cannabinoid, CB2 / Q000037:antagonists & inhibitors; D012701:Serotonin / Q000633:toxicity; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D001095:Arachidonic Acids; D001549:Benzamides; D052117:Benzodioxoles; D001892:Camphanes; D002219:Carbamates; D063388:Endocannabinoids; D004791:Enzyme Inhibitors; D008994:Monoacylglycerol Lipases; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D012701:Serotonin; D000099252:Fatty Acid Amide Hydrolases; C534333:JZL 184; C110630:SR 144528; C500528:cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester; C107594:N-(4-hydroxyphenyl)arachidonylamide