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Determination of mu-, delta- and kappa-opioid receptors in forebrain cortex of rats exposed to morphine for 10 days: Comparison with animals after 20 days of morphine withdrawal
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SYSNO ASEP 0481665 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Determination of mu-, delta- and kappa-opioid receptors in forebrain cortex of rats exposed to morphine for 10 days: Comparison with animals after 20 days of morphine withdrawal Author(s) Ujčíková, Hana (FGU-C) RID, ORCID
Hloušková, Martina (FGU-C)
Cechová, Kristína (FGU-C) RID, ORCID
Stolařová, Kateřina (FGU-C)
Roubalová, Lenka (FGU-C) RID, ORCID, SAI
Svoboda, Petr (FGU-C) RID, ORCIDArticle number e0186797 Source Title PLoS ONE. - : Public Library of Science - ISSN 1932-6203
Roč. 12, č. 10 (2017)Number of pages 22 s. Language eng - English Country US - United States Keywords morphine ; rat brain cortex ; opioid receptors ; drug withdrawal ; cholesterol Subject RIV CE - Biochemistry OECD category Biochemistry and molecular biology R&D Projects GA17-05903S GA ČR - Czech Science Foundation (CSF) GA17-07070S GA ČR - Czech Science Foundation (CSF) Institutional support FGU-C - RVO:67985823 UT WOS 000413315100039 EID SCOPUS 85031804278 DOI 10.1371/journal.pone.0186797 Annotation Chronic exposure of mammalian organism to morphine results in adaption to persistent high opioid tone through homeostatic adjustments. Our previous results indicated that in the frontal brain cortex (FBC) of rats exposed to morphine for 10 days, such a compensatory adjustment was detected as large up-regulation of adenylylcyclases I (8-fold) and II (2.5-fold). The other isoforms of AC (III-IX) were unchanged. Importantly, the increase of ACI and ACII was reversible as it disappeared after 20 days of morphine withdrawal. Changes of down-stream signaling molecules such as G proteins and adenylylcyclases should respond to and be preceded by primary changes proceeding at receptor level. Therefore in our present work, we addressed the problem of reversibility of the long-term morphine effects on mu-, delta- and kappa-OR protein levels in FBC izolated from rats exposed to increasing doses of morphine (10-40 mg/kg) for 10 days and sacrificed either 24 h (group +M10) or 20 days (group +M10/-M20) after the last dose of morphine in parallel with control animals (groups -M10 and -M10/-M20).Significant down-regulation of delta-OR form exhibiting Mw approximate 60 kDa was detected in PNS prepared from both (+M10) and (+M10/-M20) rats. However, the total immunoblot signals of mu-, delta- and kappa-OR, respectively, were unchanged. Plasma membrane marker Na, K-ATPase, actin and GAPDH were unaffected by morphine in both types of PNS. Membrane-domain marker caveolin-1 and cholesterol level increased in (+M10) rats and this increase was reversed back to control level in (+M10/-M20) rats. In FBC, prolonged exposure of rats to morphine results in minor (delta-OR) or no change (mu- and kappa-OR) of opioid receptor content. The reversible increases of caveolin-1 and cholesterol levels suggest participation of membrane domains in compensatory responses during opioid withdrawal. Analysis of reversibility of morphine effect on mammalian brain. Workplace Institute of Physiology Contact Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Year of Publishing 2018
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