New dopamine receptor, D2(Longer), with unique TG splice site, in human brain

Brain dopamine receptor agonists alleviate the signs of Parkinson's disease , while dopamine receptor antagonists alleviate hallucinations and delusion s in psychosis. The dopamine type 2 receptor (or D2) is blocked by antipsyc hotic drugs, including even the "atypical" drugs such as clozapine or remox ipride, in direct relation to their clinical potencies. Compared to the lon g form of the D2 receptor (D2(Long)), the short form (D2(Short)) may be thr ee times more sensitive to benzamide antipsychotic drugs. Hence, it is esse ntial to identify additional variants of dopamine receptors for which more selective antipsychotic drugs can be found. Although no family linkage has been found between the D2 receptor and schizophrenia, there can be brain re gion abnormalities in the RNA transcript expression of dopamine receptors. Therefore, in order to identify variant dopamine D2 receptors, we searched for mutations in the RNA transcripts for the dopamine D2 receptor in the st riatum of post-mortem brains from individuals who died with psychosis, incl uding schizophrenia. A new splice variant of the D2 receptor, D2(Longer), w ith a unique TG splice site, was found in one control brain and in two psyc hotic brains. (C) 2000 Elsevier Science B.V. All rights reserved.