Changes in the cAMP-related signal transduction mechanism in postmortem human brains of heroin addicts.
Immunoreactivities of adenylyl cyclase (AC) type I (AC-I), and basal, forskolin- and Mn2+-stimulated AC activities with or without calcium and calmodulin (Ca2+/CaM) were estimated in temporal cortex (TC)-and nucleus accumbens (NAc) membranes from brains of heroin addicts and controls. Immunoreactivity of AC-I was significantly decreased in TC from brains of heroin addicts, but that did not change in NAc. Ca2+/CaM-sensitive AC activity was significantly lower in TC from brains of heroin addicts, but that activity in NAc did not show significant difference compared with the control. Some previous reports demonstrated that Ca2+/CaM-sensitive AC activity in membranes from postmortem human brain reflected the function of AC-I. Therefore, the downregulation of AC-I in TC plays an important role in the molecular mechanism of chronic opiate addiction in human brain.
Shichinohe
S
S
Department of Neuropsychiatry, School of Medicine, Sapporo Medical University, Japan.
Ozawa
H
H
Hashimoto
E
E
Tatschner
T
T
Riederer
P
P
Saito
T
T
D000262:Adenylyl Cyclases / Q000378:metabolism; D000328:Adult; D000367:Age Factors; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D001923:Brain Chemistry / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002147:Calmodulin / Q000378:metabolism / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005576:Colforsin / Q000378:metabolism / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D005260:Female; D005615:Freezing; D003932:Heroin / Q000009:adverse effects*; D006556:Heroin Dependence / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008345:Manganese / Q000378:metabolism / Q000494:pharmacology; D009294:Narcotics / Q000009:adverse effects*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D013702:Temporal Lobe / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology
D002147:Calmodulin; D009294:Narcotics; D005576:Colforsin; D008345:Manganese; D003932:Heroin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; C106670:adenylyl cyclase 1; D002118:Calcium