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Pharmacological evidence for the involvement of adenosine triphosphate sensitive potassium channels in chloroquine-induced itch in mice

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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.

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Abbreviations

ATP-sensitive potassium channels or KATP channels:

adenosine triphosphate sensitive potassium channels

CQ:

chloroquine

DZX:

diazoxide

GLI:

glibenclamide

id:

intradermal

ip :

intraperitoneal

MIN:

minoxidil

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Author notes

  1. Both authors have contributed equally to this project.

Authors and Affiliations

  1. Brain and Spinal Injury Research Center, Neurosciences Institute, Tehran University of Medical Sciences, Tehran, Iran

    Sattar Ostadhadi, Abbas Norouzi-Javidan & Ahmad-Reza Dehpour

  2. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Sattar Ostadhadi, Arash Foroutan, Nazgol-Sadat Haddadi & Ahmad-Reza Dehpour

  3. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Sattar Ostadhadi, Arash Foroutan, Nazgol-Sadat Haddadi & Ahmad-Reza Dehpour

  4. Hematology/Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Majid Momeny, Ghazaleh Zarrinrad & Seyed Hamid Ghaffari

Authors
  1. Sattar Ostadhadi
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  2. Arash Foroutan
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  3. Nazgol-Sadat Haddadi
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  4. Abbas Norouzi-Javidan
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  8. Ahmad-Reza Dehpour
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Correspondence to Ahmad-Reza Dehpour.

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Ostadhadi, S., Foroutan, A., Haddadi, NS. et al. Pharmacological evidence for the involvement of adenosine triphosphate sensitive potassium channels in chloroquine-induced itch in mice. Pharmacol. Rep 69, 1295–1299 (2017). https://doi.org/10.1016/j.pharep.2017.05.021

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  • DOI: https://doi.org/10.1016/j.pharep.2017.05.021

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