Sc. Martin et al., Molecular identification of the human GABA(B)R2: Cell surface expression and coupling to adenylyl cyclase in the absence of GABA(B)R1, MOL CELL NE, 13(3), 1999, pp. 180-191
We have identified a gene encoding a GABA(B) receptor, the human GABA(B)R2,
located on chromosome 9q22.1, that is distinct from the recently reported
rat GABA(B)R1. GABA(B)R2 structurally resembles GABA(B)R1 (35% identity), h
aving seven transmembrane domains and a large extracellular region, but dif
fers in having a longer carboxy-terminal tail. GABA(B)R2 is localized to th
e cell surface in transfected COS cells, and negatively couples to adenylyl
cyclase in response to GABA, baclofen, and 8-aminopropyl(methyl)phosphinic
acid in CHO cells lacking GABA(B)R1. Baclofen action is inhibited by the G
ABA(B)R antagonist, 2-hydroxysaclofen. The human GABA(B)R2 and GABA(B)R1 ge
nes are differentially expressed in the nervous system, with the greatest d
ifference being detected in the striatum in which GABA(B)R1 but not GABA(B)
R2 mRNA transcripts are detected. GABA(B)R2 and GABA(B)R1 mRNAs are also co
expressed in various brain regions such as the Purkinje cell layer of the c
erebellum. Identification of a functional homomeric GABA(B)R2 coupled to ad
enylyl cyclase suggests that the complexity of GABA(B) pharmacological data
is at least in part due to the presence of more than one receptor and open
s avenues for future research leading to an understanding of metabotropic G
ABA receptor signal transduction mechanisms.