Differential alteration of adenylyl cyclase subtypes I, II, and V/VI in postmortem human brains of heroin addicts.

In animal and culture cell experiments, the upregulation of cAMP-related signal transduction after chronic opioid administration has been hypothesized to be an adaptive change of the molecular mechanism to maintain homeostasis in intracellular signals downstream from opioid receptors. Herein, we have examined the quantitative changes of three adenylyl cyclase (AC) subtypes (I, II, and V/VI) in temporal cortex membranes from brains of heroin addicts and age-matched controls by immunoblotting. 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 differential regulation of AC subtypes occurs and that AC-I may play an important role in the signal transduction for opiate-induced tolerance and dependence mechanisms in human brain cortex.