Shorter variants of the D3 dopamine receptor produced through various patterns of alternative splicing

Using Polymerase Chain Reaction amplification of mRNAs from several areas of rat brain we have shown the occurrence of two shorter transcripts of the dopamine D3 receptor gene, in addition to that corresponding to the D3 receptor. Cloning and sequencing of these transcripts, together with the establishment of the exon-intron organization of the D3 receptor gene, shown these transcripts to result from different processes of alternative splicing. The first transcript encodes a 100 amino acid protein, being produced by splicing of an exon whose absence deletes the third transmembrane domain and gives rise downstream to a frameshift in the open reading frame. In the second transcript, an in frame 54 bp deletion is produced by splicing occurring at an internal acceptor site, suppressing half of the second extracellular loop and a small sequence in the fifth transmembrane domain. This transcript was stably expressed in CHO cells which, however, failed to reveal any dopaminergic ligand binding activity. The functional significance and possible role of these shorter variants of the dopamine D3 receptor in cell signalling remain to be established.