title: Involvement of nitric oxide in serotonin-induced scratching in mice.
abstract: BACKGROUND
  Serotonin is a pruritogenic substance in humans and animals, but the mechanisms of action through which serotonin induces itch response are not yet understood.
  
  
  OBJECTIVE
  To examine the possible role of nitric oxide (NO) in the profile of scratching behaviour due to intradermal injection of serotonin in mice.
  
  
  METHODS
  Intradermal injection of serotonin (14.1-235 nmol per site) into the nape of the neck was used to elicit itch in mice. Scratching behaviour was evaluated by counting the number of bouts during 60 min after injection. To determine the possible involvement of the nitrergic system in serotonin-induced scratching, L-NG-nitroarginine methyl ester [L-NAME; a nonselective nitric oxide synthase (NOS) inhibitor], aminoguanidine [a selective inducible (i)NOS inhibitor] and L-arginine (an NO precursor) were administered intraperitoneally to control and serotonin-injected animals.
  
  
  RESULTS
  Intradermal serotonin caused scratching in mice with a bell-shaped dose-response correlation, and the peak effective dose was 141 nmol per site. The majority of scratching bouts in animals occurred 5-10 min after injection. Ineffective doses of L-NAME (3 mg/kg IP) and aminoguanidine (100 mg/kg IP) decreased the scratching induced by intradermal serotonin injection in animals (P < 0.001 and P < 0.001), while an subeffective dose of L-arginine (100 mg/kg IP) augmented the scratching effect of serotonin (P < 0.001).
  
  
  CONCLUSIONS
  We show for the first time that the scratching induced by intradermal serotonin is mediated by NOS, especially iNOS, activation. We conclude that NO may play a role in mediating itch responses. NO and NOS could be new targets for antipruritic agents.
authors.affiliation: Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.|Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: S
authors.initials: S
authors.lastname: Ostadhadi
authors.affiliation: Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.|Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: A
authors.initials: A
authors.lastname: Haj-Mirzaian
authors.affiliation: Cutaneous Biology Research Center, Massachusetts General Hospital, Charlestown, MA, USA.
authors.forename: E
authors.initials: E
authors.lastname: Azimi
authors.affiliation: Skin and Stem cell Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: P
authors.initials: P
authors.lastname: Mansouri
authors.affiliation: Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.|Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: A R
authors.initials: AR
authors.lastname: Dehpour
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors; D006146:Guanidines / Q000494:pharmacology; D007271:Injections, Intradermal; D008297:Male; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011537:Pruritus / Q000139:chemically induced* / Q000503:physiopathology; D012701:Serotonin; D017366:Serotonin Receptor Agonists
chemical_list: D004791:Enzyme Inhibitors; D006146:Guanidines; D017366:Serotonin Receptor Agonists; D009569:Nitric Oxide; D012701:Serotonin; D001120:Arginine; D019001:Nitric Oxide Synthase; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester