Schizophrenia: Normal Sequence in the Dopamine D₂ Receptor Region that Couples to G-Proteins. DNA Polymorphisms in D₂

Abstract

Because dopamine (DA) D₂ receptors are a target in neuroleptic therapy and have been found to be elevated in schizophrenia, the human DA D₂ receptor gene was examined for possible abnormalities in schizophrenia. Moreover, since D₂ receptors in psychosis have a reduced coupling to D₁ receptors, the cytoplasmic third loop of D₂ was chosen for deoxyribonucleic acid (DNA) sequencing, since this region is essential for coupling to G-proteins. This region also contains exon 5, which is expressed in the long form of D₂, but not in the short form of D₂. In eight schizophrenia cases, this region had normal exon sequences (exons 4, 5 and 6), and normal sequences at its intron-exon junctions. However, exon 6 contained three DNA polymorphic base changes, and introns 4 and 5 revealed three missing bases and two polymorphic base changes, none of which would be expected to alter the D₂ receptor protein in schizophrenia.

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