title: Chloroquine-induced scratching is mediated by NO/cGMP pathway in mice.
abstract: Chloroquine (CQ), a 4-aminoquinoline drug, has long been used in the treatment and prevention of malaria. However its side effect generalized pruritus contributes to treatment failures, and consequently results in the development of chloroquine resistant strains of Plasmodium falciparum. It was proposed that the administration of CQ correlated with increase in nitric oxide (NO) production. Nitric oxide is involved in some pruritic disorders such as atopic dermatitis, psoriasis and scratching behavior evoked by pruritogens like substance P. Therefore, the aim of this study was to investigate the involvement of NO/cGMP pathway in CQ-induced scratching in mice. Scratching behaviors were recorded by a camera after intradermal (ID) injection of CQ in the shaved rostral back of the mice. The results obtained show that CQ elicited scratching in a dose-dependent manner with a peak effective dose of 400μg/site. Injection of non-specific NOS inhibitor, N-nitro-l-arginine methyl ester or neuronal NOS selective inhibitor and 7-nitroindazole, reduced CQ-induced scratching significantly. On the other hand, administration of aminoguanidine as inducible NOS inhibitor has no inhibitory effect on this behavior. Also, injection of l-arginine as a precursor of NO significantly increased this response. Conversely, accumulation of cGMP by sildenafil as a selective phosphodiesterase type 5 inhibitor, potentiated the scratching behavior by CQ. This study therefore shows that CQ-induced scratching behavior is mediated by the NO/cGMP pathway.
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; Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Arash
authors.initials: A
authors.lastname: Foroutan
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: Nazgol Sadat
authors.initials: NS
authors.lastname: Haddadi
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: Sattar
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: Narges
authors.initials: N
authors.lastname: Sistany
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; Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: dehpoura@sina.tums.ac.ir.
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Dehpour
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D002738:Chloroquine / Q000009:adverse effects*; D006152:Cyclic GMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D011537:Pruritus / Q000139:chemically induced* / Q000503:physiopathology
chemical_list: D009569:Nitric Oxide; D002738:Chloroquine; D006152:Cyclic GMP
keywords: Chloroquine; Cyclic GMP; Mice; Nitric oxide; Scratching