title: Anti-pruritic activity of pioglitazone on serotonin-induced scratching in mice: possible involvement of PPAR-gamma receptor and nitric oxide.
abstract: Pioglitazone is a member of peroxisome proliferator-activated receptor gamma (PPARγ) agonists, particularly used in management of type II diabetes. However it also has effects in some dermatological disorders. The current study was designed to investigate the effects of oral administration of pioglitazone and the association of nitric oxide, in serotonin-induced scratching in mice. In order to produce the scratching activity, serotonin (141 nm/site) was administered intradermally in the nape of the neck. Pioglitazone in concentrations of 10, 20, 40 and 80 mg/kg, was peroral administered (p.o) as a single dose, 4 h before the serotonin injection. PPAR-γ antagonist, GW9662 (2 mg/kg, i.p); a non-specific nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 1 mg/kg, i.p); or a nitric oxide precursor, L-arginine (100 mg/kg, i.p.); adminstrated 15 min before pioglitazone were analyzed for anti-scratching activity. Results obtained showed that pioglitazone (40 and 80 mg/kg, p.o) reduced the scratching in a dose-dependent manner. GW9662 inverted the anti-scratching effect of pioglitazone (80 mg/kg). Acute dose of L-NAME (1 mg/kg, i.p) also prevented the anti-scratching property of pioglitazone (80 mg/kg, p.o); although L-arginine was used in sub-effective dose (100 mg/kg, i.p), however it potentiated the anti-scratching behavior when co-injected with pioglitazone (20 mg/kg, p.o). The results indicate that acute pioglitazone has an anti-scratching effect on serotonin-induced scratching in mice. It is concluded that anti-scratching outcome of acute pioglitazone is initiated via activation of PPAR-γ receptor and to some extent by the NO pathway.
authors.affiliation: Experimental Medicine Research Center, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Milad
authors.initials: M
authors.lastname: Shafizadeh
authors.affiliation: Experimental Medicine Research Center, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Armin
authors.initials: A
authors.lastname: Rajaba
authors.affiliation: Experimental Medicine Research Center, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, International campus, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Imran khan
authors.affiliation: Experimental Medicine Research Center, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Sattar
authors.initials: S
authors.lastname: Ostadhadi
authors.affiliation: Food and Drug Research Center, Ministry of Health and Medical Education,Tehran, Iran.
authors.forename: Hosein
authors.initials: H
authors.lastname: Rastegar
authors.affiliation: Experimental Medicine Research Center, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: dehpoura@sina.tums.ac.ir.
authors.forename: Ahmadreza
authors.initials: A
authors.lastname: Dehpour
mesh_terms: D000818:Animals; D001120:Arginine / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D008297:Male; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000378:metabolism / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D047495:PPAR gamma / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000077205:Pioglitazone; D012701:Serotonin / Q000378:metabolism*; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: D047495:PPAR gamma; D045162:Thiazolidinediones; D009569:Nitric Oxide; D012701:Serotonin; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester; D000077205:Pioglitazone
keywords: Mice; Nitric oxide; Pioglitazone; Scratching; Serotonin