{"title":"The possible involvement of KATP channels in cholestatic pruritus in mice","authors":"Arya Afrooghe, Maryam Shayan, Nazgol-Sadat Haddadi, Asma Rashki, Shahabaddin Solaimanian, Maryam Shokrian Zeini, Ahmad-Reza Dehpour","doi":"10.1007/s13596-024-00802-w","DOIUrl":null,"url":null,"abstract":"<div><p>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 (K<sub>ATP</sub> channels) contribute to transmitting signals, including itch. Here, we investigated the role of K<sub>ATP</sub> channels in cholestatic pruritus in mice induced by bile duct ligation (BDL). K<sub>ATP</sub> 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 K<sub>ATP</sub> channel (<i>Kcnj8</i> and <i>Kcnj11</i>) via RT-qPCR analysis. We detected increased scratching responses in cholestatic mice regarding intradermal vehicle injection, representing cholestatic pruritus. K<sub>ATP</sub> 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, K<sub>ATP</sub> 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 <i>Kcnj11</i> in BDL mice. We conclude that K<sub>ATP</sub> channels are possibly involved in cholestatic itch. Further studies are needed to elucidate the other associations between cholestasis and itch.</p></div>","PeriodicalId":7613,"journal":{"name":"Advances in Traditional Medicine","volume":"25 3","pages":"611 - 619"},"PeriodicalIF":1.3000,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advances in Traditional Medicine","FirstCategoryId":"1085","ListUrlMain":"https://link.springer.com/article/10.1007/s13596-024-00802-w","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
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.
期刊介绍:
Advances in Traditional Medicine (ADTM) is an international and peer-reviewed journal and publishes a variety of articles including original researches, reviews, short communications, and case-reports. ADTM aims to bridging the gap between Traditional knowledge and medical advances. The journal focuses on publishing valid, relevant, and rigorous experimental research and clinical applications of Traditidnal Medicine as well as medical classics. At the same time, the journal is devoted to communication among basic researcher and medical clinician interested in the advancement of Traditional Medicine. Topics covered by the journal are: Medical Classics & History; Biomedical Research; Pharmacology & Toxicology of Natural Products; Acupuncture & Moxibustion; Sasang Constitutional Medicine; Diagnostics and Instrumental Development; Clinical Research. ADTM is published four times yearly. The publication date of this journal is 30th March, June, September, and December.