title: Up-regulation of adenylylcyclases I and II induced by long-term adaptation of rats to morphine fades away 20 days after morphine withdrawal.
abstract: BACKGROUND
  Activation of adenylyl cyclase (AC) by prolonged exposure of mammalian organism to morphine was demonstrated in previous studies of mechanism of action of this drug. However, expression level of individual AC isoforms was not analyzed in crucial cell structure, plasma membrane (PM).
  
  
  METHODS
  Rats were adapted to morphine for 10 days and sacrificed 24h (group+M10) or 20 days (+M10/-M20) after the last dose. Control animals were sacrificed in parallel with morphine-treated (groups-M10 and (-M10/-M20)). Percoll®-purified PM were isolated from brain cortex and analyzed by immunoblotting and specific radioligand binding.
  
  
  RESULTS
  ACI (ACII) was increased 8× (2.5×) in morphine-adapted rats (+M10) when compared with controls (-M10). Increase of ACI and II by long-term adaptation to increasing doses of morphine represented a specific effect as the amount of ACIII-ACIX, of prototypical PM marker, Na, K-ATPase and of trimeric G protein α and β subunits was unchanged. Increase of ACI and II was not detected in PM isolated from group (+M10/-M20). Thus, the marked increase of ACI and ACII faded away 20 days since the last dose of morphine.
  
  
  CONCLUSIONS
  We assume that the specific increase in expression level of ACI and ACII in brain cortex of morphine-adapted rats proceeds as a compensatory, homeostatic response to prolonged exposure to inhibitory drug, morphine.
  
  
  CONCLUSIONS
  Our findings demonstrate that the dramatic and specific change of the crucial component of the opioid receptor cascade in brain cortex, manifested as an increase in PM level of ACI and II, is reversible.
authors: Institute of Physiology, v.v.i., Academy of Sciences of the Czech Republic, Videnska 1083, 14220 Prague 4, Czech Republic.
authors: Hana
authors: H
authors: Ujcikova
authors: Katerina
authors: K
authors: Dlouha
authors: Lenka
authors: L
authors: Roubalova
authors: Miroslava
authors: M
authors: Vosahlikova
authors: Dmytro
authors: D
authors: Kagan
authors: Petr
authors: P
authors: Svoboda
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D004591:Electrophoresis, Polyacrylamide Gel; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D009020:Morphine / Q000009:adverse effects*; D051381:Rats; D017208:Rats, Wistar; D017465:Receptors, Opioid, delta / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013375:Substance Withdrawal Syndrome; D015854:Up-Regulation
chemical_list: D007527:Isoenzymes; D017465:Receptors, Opioid, delta; D009020:Morphine; D000262:Adenylyl Cyclases; D000254:Sodium-Potassium-Exchanging ATPase