DIFFERENTIAL ALTERATION OF ADENYLYL-CYCLASE SUBTYPE-I, SUBTYPE-II, AND SUBTYPE-V VI IN POSTMORTEM HUMAN BRAINS OF HEROIN-ADDICTS/

In animal and culture cell experiments, the upregulation of cAMP-relat ed signal transduction after chronic opioid administration has been hy pothesized to be an adaptive change of the molecular mechanism to main tain homeostasis in intracellular signals downstream from opioid recep tors. Herein, we have examined the quantitative changes of three adeny lyl cyclase (AC) subtypes (I, II, and V/VI) in temporal cortex membran es from brains of heroin addicts and age-matched controls by immunoblo tting. The immunoreactivity of AC-I decreased significantly (p < 0.05) in heroin addicts, compared with controls; whereas those of AC-II and AC-V/VI were not changed. The present findings indicate that differen tial regulation of AC subtypes occurs and that AC-I may play an import ant role in the signal transduction for opiate-induced tolerance and d ependence mechanisms in human brain cortex.