A second molecular form of D2 dopamine receptor in rat and bovine caudate nucleus

Abstract

Overexpression of the D2 dopamine receptor has been proposed to be part of the pathology of schizophrenia. The isolation of a D2 dopamine receptor clone has assisted the molecular characterization of D2 receptor. We have now isolated an identical rat clone along with two other clones--a second related rat clone (RD-2in) and a homologous bovine clone (BD-2in), both of which contain an insert encoding an additional 29 amino acids relative to the original rat clone (RD-2o). All three clones encode D2 receptor binding sites when expressed in COS-7 cells. The amino-acid insert encoded by D-2in lies in the domain of the receptor believed to interact with the GTP-binding proteins (G proteins) of various signal transduction pathways. By using oligonucleotide probes specific for either D-2o or D-2in RNA transcripts, we have found that the level of expression of the D-2in-encoded form of the receptor is seven times that of the D-2o form in the caudate nucleus, the richest brain source of D2 receptors.

Another mechanism for creating diversity in gamma-aminobutyrate type A receptors: RNA splicing directs expression of two forms of gamma 2 phosphorylation site.

“…Alternative RNA splicing as a mechanism for creating diversity has been reported for other receptor systems. Recent studies have demonstrated that two forms of D2 dopamine receptor exist as a result of alternative RNA splicing from a single gene (24)(25)(26)(27). The physiological role of the two forms, which differ by a 29-amino acid insertion in the third cytoplasmic loop, has yet to be determined.…”

Dopamine D2 Long Receptor-Deficient Mice Display Alterations in Striatum-Dependent Functions

“…Two isoforms of the D2 receptor [the long form (D2L) and the short form (D2S)] have been identified (Bunzow et al, 1988;Dal Toso et al, 1989;Giros et al, 1989;Monsma et al, 1989;Chio et al, 1990;Mack et al, 1991). The D2L and D2S receptors are generated from the same gene by alternative splicing.…”

“…Schizophrenic patients exhibit psychotic symptoms, which may partially result from dysfunction of the mesocortical and hippocampal dopamine (DA) systems (Carlsson and Carlsson, 1990;Jaskiw and Weinberger, 1992). The drugs typically used to treat schizophrenia and Parkinson's disease are D2 antagonists or agonists, respectively, suggesting that the D2 receptor plays an important role in these two neuropsychiatric diseases.Two isoforms of the D2 receptor [the long form (D2L) and the short form (D2S)] have been identified (Bunzow et al, 1988;Dal Toso et al, 1989;Giros et al, 1989;Monsma et al, 1989;Chio et al, 1990;Mack et al, 1991). The D2L and D2S receptors are generated from the same gene by alternative splicing.…”

In vitro pharmacological profile of YM‐43611, a novel D2‐like receptor antagonist with high affinity and selectivity for dopamine D3 and D4 receptors

“…The rat D2L cDNA (the exon 6-containing form) and the rat D3 cDNA were cloned by reverse transcription-polymerase chain reaction (RT-PCR) amplification according to the methods of Chio et al (1990) and Sokoloff et al (1990), respectively. The cloned cDNAs were then ligated into the expression vector pVYl containing dihydrofolate reductase (dhfr) gene as a selective marker.…”