Guanine nucleotides distinguish between two dopamine receptors

• DOI: 10.1038/278577a0
• Publication Date: 2005-08-02T12:34:19Z
• Authors: IAN CREESE; TED USDIN; SOLOMON H. SNYDER
• Keywords: Spiperone

BEHAVIOURAL1 and neurophysiological2 data suggest the existence of more than one dopamine receptor in the brain3. Differences in drug specificity of the dopamine-sensitive adenylate cyclase and dopamine receptors labelled by the butyrophenones, 3H-haloperidol or 3H-spiroperidol, indicate that the cyclase and the binding sites may, in part, involve distinct receptors4,5. Lesion studies directly demonstrate the existence of physically distinct dopamine receptors in the corpus striatum6. Kainic acid microinjections, which selectively destroy intrinsic neurones in the corpus striatum, almost totally deplete the dopamine-sensitive adenylate cyclase while producing only a 40–50% decline in 3H-haloperidol or 3H-spiroperidol binding. Most of the remaining 3H-haloperidol or 3H-spiroperidol binding is lost following cerebral cortex ablation, which removes a major neuronal input to the corpus striatum, indicating that these binding sites are localised to axons and terminals of the cortico-striate projection6. As the dopamine-sensitive adenylate cyclase is not reduced by cerebral cortex ablation, the cortico-striate dopamine receptors do not seem to be linked to adenylate cyclase. Whether or not the 3H-butyrophenone binding sites destroyed by kainic acid represent the same dopamine receptors as those linked to adenylate cyclase has not been clear. Guanine nucleotides regulate binding at several hormone and neurotransmitter receptors, especially those associated with adenylate cyclase7–13. Previously, we14–16 and others17 showed that dopamine receptor binding of 3H-agonists and 3H-antagonists can be regulated by guanine nucleotides. We now report that kainic acid lesions abolish the sensitivity of dopamine receptor binding to guanine nucleotides. Thus, 3H-spiroperidol and 3H-apomorphine binding sites involve two dopamine receptors, only one of which is regulated by guanine nucleotides.