Pharmacological Evidence for the Involvement of Adenosine Triphosphate Sensitive Potassium Channels in Chloroquine-Induced Itch in Mice Publisher Pubmed



Ostadhadi S^{1, 2, 3} ; Foroutan A^{2, 3} ; Haddadi NS^{2, 3} ; Norouzijavidan A¹ ; Momeny M⁴ ; Zarrinrad G⁴ ; Ghaffari SH⁴ ; Dehpour AR^{1, 2, 3} Show Affiliations
Source: Pharmacological Reports Published:2017

Abstract

Background Chloroquine (CQ) evokes itch in human and scratching behavior in rodents through a histamine-independent pathway. Chloroquine directly excites peripheral sensory neurons which convey itch signals to the central nervous system. It has been revealed that ATP-sensitive potassium channels (KATP channels) are important in regulating neuronal excitability. Thus, we aimed to investigate the involvement of KATP channels in CQ-induced itch which may also reveal a linkage between metabolic state of cells and itch. Methods Intradermal (id) injection of CQ at dose of 400 μg/site induces the scratching behavior. KATP channel openers, diazoxide (DZX) and minoxidil (MIN), and a KATP channel blocker, glibenclamide (GLI), were administered intraperitoneally (ip) before CQ. Then the behavior was recorded for 30 min, in an unmanned condition, and the scratching bouts were counted by an expert observer who was blinded to the experiments. Furthermore, quantitative reverse transcription-PCR (qRT-PCR) was used to investigate the possible changes in dermal expression of Kcnj8 and Kcnj11, the genes encoding the KATP channels. Results Our results show that either DZX (10 mg/kg, ip) or MIN (10 mg/kg, ip) significantly attenuated CQ-induced scratching behavior in mice. Moreover, pretreatment with GLI (3 mg/kg, ip) significantly reversed the anti-pruritic effects of DZX and MIN. Our finding of qRT-PCR analysis also show that the expression of Kcnj8 is decreased after CQ injection. Conclusions We suggest that KATP channels are possibly involved in CQ-induced itch. While, further studies will be significant to better elucidate the association of metabolic state of cells and itch. © 2017