Dopamine D2 receptor (DRD2) is one of the five dopamine receptors with seve
n transmembrane domains that are coupled to the G protein. We have cloned a
nd characterized the genomic and cDNA sequences of the canine DRD2 gene, wh
ich are 12.7 and 2.7 kb in size, respectively. The genomic DNA is composed
of seven exons and six introns, encoding a 443 amino acid protein with 95%
amino acid identity to other mammalian D2 receptors. A length polymorphism
was detected in intron 3 of the receptor gene. We also characterized altern
atively spliced forms of DRD2 cDNAs, DRD2L and DRD2S. They showed a higher
level of expression in midbrain and thalamus. The ratio between the long an
d short form is similar in RT-PCR reaction. In human and rodent, the same t
wo spliced forms are known to be coupled to G(i)-type heterotrimeric GTP bi
nding protein, thereby opening an inwardly rectifying potassium channel, GI
RK1. When the canine DRD2L and DRD2S were heterologously expressed in Xenop
us oocytes, both forms activated GIRK1 potassium channels through coupling
with Gi protein. This activation was dose-dependent, demonstrating its liga
nd specificity. (C) 2000 Elsevier Science B.V. All rights reserved.