Počet záznamů: 1  

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

  1. 1. 0481665 - FGU-C 2018 RIV US eng J - Článek v odborném periodiku
    Ujčíková, Hana - Hloušková, Martina - Cechová, Kristína - Stolařová, Kateřina - Roubalová, Lenka - Svoboda, Petr
    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.
    PLoS ONE. Roč. 12, č. 10 (2017), č. článku e0186797. E-ISSN 1932-6203
    Grant CEP: GA ČR(CZ) GA17-05903S; GA ČR(CZ) GA17-07070S
    Institucionální podpora: RVO:67985823
    Klíčová slova: morphine * rat brain cortex * opioid receptors * drug withdrawal * cholesterol
    Kód oboru RIV: CE - Biochemie
    Obor OECD: Biochemistry and molecular biology
    Impakt faktor: 2.766, rok: 2017

    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.
    Trvalý link: http://hdl.handle.net/11104/0277200