title: Spatial distribution of GABA(B)R1 receptor mRNA and binding sites in the rat brain.
abstract: A gamma-aminobutyric acid (GABA)(B) receptor (named GABA(B)R1) has been recently cloned in the rat and human brain and two variants generated by alternative RNA splicing were identified. In the present study, we addressed the question as to whether these variants contribute to the diversity of GABA(B) receptor-mediated physiological responses and constitute real receptor subtypes with distinct functions. To this aim, we have mapped the GABA(B)R1 (R1a) and GABA(B)R1b (R1b) transcript distribution in the rat brain using in situ hybridization. We have compared the mRNA distribution with the distribution of [(3)H]CGP54626-labeled binding GABA(B)R1 receptor sites as assessed in adjacent cryosections by quantitative autoradiography. We found that GABA(B) receptor transcripts and binding sites are expressed in the brain in almost all neuronal cell populations. Expression in glial cells, if any, is marginal. We observed a good parallelism between GABA(B)R1 mRNA transcripts and binding sites in broad neuroanatomical entities with highest densities in hippocampus, thalamic nuclei, and cerebellum. By contrast, R1a and R1b transcripts exhibit marked differences in their regional and cellular distribution pattern. A typical example is the cerebellum with an almost exclusive expression of R1b in the Purkinje cells and of R1a in the granule, stellate, and basket cells. Data pointing at a pre- versus postsynaptic localization for R1a and R1b, respectively, at some neuronal sites are presented.
authors.affiliation: Novartis Pharma AG, Nervous System, CH-4002 Basel, Switzerland. serge_francois.bischoff@pharma.novartis.com
authors.forename: S
authors.initials: S
authors.lastname: Bischoff
authors.forename: S
authors.initials: S
authors.lastname: Leonhard
authors.forename: N
authors.initials: N
authors.lastname: Reymann
authors.forename: V
authors.initials: V
authors.lastname: Schuler
authors.forename: R
authors.initials: R
authors.lastname: Shigemoto
authors.forename: K
authors.initials: K
authors.lastname: Kaupmann
authors.forename: B
authors.initials: B
authors.lastname: Bettler
mesh_terms: D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000166:cytology / Q000502:physiology*; D001923:Brain Chemistry / Q000502:physiology*; D001931:Brain Mapping; D018755:GABA Agonists / Q000378:metabolism; D017403:In Situ Hybridization; D008297:Male; D009474:Neurons / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000378:metabolism; D011689:Purkinje Cells / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D018080:Receptors, GABA-B / Q000096:biosynthesis*
chemical_list: D018755:GABA Agonists; D009943:Organophosphorus Compounds; D012333:RNA, Messenger; D018080:Receptors, GABA-B; C107353:CGP 54626