The Possible Involvement of Katp Channels in Cholestatic Pruritus in Mice Publisher



A Afrooghe ARYA ; M Shayan MARYAM ; Ns Haddadi Nazgol SADAT ; A Rashki ASMA ; S Solaimanian SHAHABADDIN ; Ms Zeini Maryam SHOKRIAN ; Ar Dehpour Ahmad REZA
Source: Advances in Traditional Medicine Published:2025

Abstract

Cholestatic itch dramatically impairs the quality of life of affected patients; however, the therapeutic choices are limited and far from sufficient. ATP-sensitive potassium channels (KATP channels) contribute to transmitting signals, including itch. Here, we investigated the role of KATP channels in cholestatic pruritus in mice induced by bile duct ligation (BDL). KATP channel openers (diazoxide and minoxidil) and blockers (glibenclamide) were administered via the intraperitoneal route in BDL and sham-operated (Sham) mice. After the open-field test, the scratching behavior in response to the intradermal vehicle injection was videotaped for one hour. We investigated the probable alterations in the dermal expression of genes encoding the KATP channel (Kcnj8 and Kcnj11) via RT-qPCR analysis. We detected increased scratching responses in cholestatic mice regarding intradermal vehicle injection, representing cholestatic pruritus. KATP channel openers, diazoxide (10 mg/kg, i.p.), and minoxidil (10 mg/kg, i.p.) attenuated scratching responses in the bile duct ligated mice. On the other hand, KATP channel blocker glibenclamide (3 mg/kg, i.p.) intensified the scratching behavior. Moreover, pre-treatment with the sub-effective dose of glibenclamide (1 mg/kg, i.p.) reversed the anti-pruritic effects of diazoxide (10 mg/kg, i.p.) and minoxidil (10 mg/kg, i.p.). The open-field test revealed that the scratching behavior was not affected by locomotor activity. Our finding of RT-qPCR analysis also showed an increase in the expression of Kcnj11 in BDL mice. We conclude that KATP channels are possibly involved in cholestatic itch. Further studies are needed to elucidate the other associations between cholestasis and itch. © 2025 Elsevier B.V., All rights reserved.