The dopamine D2 receptor: two molecular forms generated by alternative splicing

• Published in: The EMBO journal Vol. 8; no. 13; pp. 4025 - 4034
• Main Authors: Dal Toso, R., Sommer, B., Ewert, M., Herb, A., Pritchett, D.B., Bach, A., Shivers, B.D., Seeburg, P.H.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 20-12-1989
• Subjects: Amino Acid Sequence; Autoradiography; Base Sequence; Biological and medical sciences; Cloning, Molecular; DNA - genetics; DNA - isolation & purification; Exons; Fundamental and applied biological sciences. Psychology; Gene expression; Genes; Genetic Vectors; Humans; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Mutation; Nucleic Acid Hybridization; Oligonucleotide Probes; Pituitary Gland - metabolism; Plasmids; Polymerase Chain Reaction; Receptors, Dopamine - genetics; Receptors, Dopamine D2; Restriction Mapping; RNA Splicing; RNA, Messenger - analysis; RNA, Messenger - genetics; Sulfur Radioisotopes; Human; Brain; Ligand binding; Molecular hybridization; Molecular form; Radiolabelling; Rat; Nucleotide sequence; In situ; Rodentia; Gene expression; Polymerase chain reaction; Vertebrata; Mammalia; Exon; Messenger RNA; D2 Dopamine receptor; Complementary DNA; Deletion; Pituitary gland; Molecular cloning; Aminoacid sequence
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1002/j.1460-2075.1989.tb08585.x

Cloned human dopamine D2 receptor cDNA was isolated from a pituitary cDNA library and found to encode an additional 29 amino acid residues in the predicted intracellular domain between transmembrane regions 5 and 6 relative to a previously described rat brain D2 receptor. Results from polymerase chain reactions as well as in situ hybridization revealed that mRNA encoding both receptor forms is present in pituitary and brain of both rat and man. The larger form was predominant in these tissues and, as shown in the rat, expressed by dopaminergic and dopaminoceptive neurons. Analysis of the human gene showed that the additional peptide sequence is encoded by a separate exon. Hence, the two receptor forms are generated by differential splicing possibly to permit coupling to different G proteins. Both receptors expressed in cultured mammalian cells bind [3H]spiperone with high affinity and inhibit adenylyl cyclase, as expected of the D2 receptor subtype.