The Possible Involvement of KATP Channels in Cholestatic Pruritus in Mice

Abstract

Background 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. Taking together the modulatory effects of KATP channels on neural excitation and the neurogenic origin of cholestatic itch, we investigated the role of these channels in cholestatic pruritus in mice induced by bile duct ligation. Results We detected increased scratching responses in cholestatic mice regarding intradermal vehicle injection, representing cholestatic pruritus. KATP channel openers, diazoxide (10 mg/kg, intraperitoneal), and minoxidil (10 mg/kg, intraperitoneal) attenuated scratching responses in the bile duct ligated mice. On the other hand, KATP channel blocker glibenclamide (3 mg/kg intraperitoneal) intensified the scratching behavior. Moreover, pre-treatment with the sub-effective dose of glibenclamide (1 mg/kg, intraperitoneal) reversed the anti-pruritic effects of diazoxide (10 mg/kg, intraperitoneal) and minoxidil (10 mg/kg intraperitoneal). The open-field test revealed that the scratching behavior was not affected by locomotor activity. Our finding of Quantitative reverse transcription-polymerase chain reaction analysis also showed an increase in the expression of Kcnj11 in bile-duct ligated mice. Conclusions We conclude that ATP-sensitive potassium channels are possibly involved in cholestatic itch. Further studies are needed to elucidate the other associations between cholestasis and itch.