Dopamine D-1-stimulated adenylyl cyclase activity in cerebral cortex of autopsied human brain

Although the cerebral cortical dopamine D-1 receptor is considered to play a role in normal and abnormal brain function, little information is availab le on its characteristics in human brain. We compared dopamine-stimulated a denylyl cyclase (AC) activity in homogenates of cerebral cortex (frontal, t emporal, parietal, occipital and cingulate cortex) of autopsied brain of ne urologically normal subjects to that in striatum. Cerebral cortical AC acti vity was modestly and dose-dependently stimulated by dopamine (maximal 20-3 0%) with low muM EC50s and such stimulation was inhibited by the selective dopamine D-1 receptor antagonist SCH23390. The magnitude of the maximal sti mulation by dopamine was similar in autopsied and biopsied cerebral cortex. The extent of maximal stimulation was similar to that in dopamine-rich str iatum (caudate, putamen and nucleus accumbens), despite much lower density of dopamine D-1 receptors in cerebral cortex vs. striatum. The EC50 for dop amine stimulation in cerebral cortex (similar to 1 muM) was lower than that for caudate and putarnen (similar to 3 muM). No detectable dopamine stimul ation was observed in cerebellar cortex, thalamus or hippocampus. Dopamine stimulation in both cerebral cortex and striatum was independent of calcium activation. We conclude that dopamine stimulated AC can be measured in cer ebral cortex of human brain allowing for the possibility that this process can be examined in human brain disorders in which dopaminergic abnormalitie s are suspected. (C) 2001 Elsevier Science Ltd. All rights reserved.