GABAB receptor isoforms GBR1a and GBR1b, appear to be associated with pre‐ and post‐synaptic elements respectively in rat and human cerebellum

GABAB receptor isoforms GBR1a and GBR1b, appear to be associated with pre‐ and post‐synaptic... Metabotropic γ‐aminobutyric acid (GABA) receptors, GABAB, are coupled through G‐proteins to K+ and Ca2+ channels in neuronal membranes. Cloning of the GABAB receptor has not uncovered receptor subtypes, but demonstrated two isoforms, designated GBR1a and GBR1b, which differ in their N terminal regions. In the rodent cerebellum GABAB receptors are localized to a greater extent in the molecular layer, and are reported to exist on granule cell parallel fibre terminals and Purkinje cell (PC) dendrites, which may represent pre‐ and post‐synaptic receptors. The objective of this study was to localize the mRNA splice variants, GBR1a and GBR1b for GABAB receptors in rat cerebellum, for comparison with the localization in human cerebellum using in situ hybridization. Receptor autoradiography was performed utilizing [3H]‐CGP62349 to localize GABAB receptors in rat and human cerebellum. Radioactively labelled oligonucleotide probes were used to localize GBR1a and GBR1b, and by dipping slides in photographic emulsion, silver grain images were obtained for quantification at the cellular level. Binding of 0.5 nM [3H]‐CGP62349 demonstrated significantly higher binding to GABAB receptors in the molecular layer than the granule cell (GC) layer of rat cerebellum (molecular layer binding 200±11% of GC layer; P<0.0001). GBR1a mRNA expression was found to be predominantly in the GC layer (PC layer grains 6±6% of GC layer grains; P<0.05), and GBR1b expression predominantly in PCs (PC layer grains 818±14% of GC layer grains; P<0.0001). The differential distribution of GBR1a and GBR1b mRNA splice variants for GABAB receptors suggests a possible association of GBR1a and GBR1b with pre‐ and post‐synaptic elements respectively. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png British Journal of Pharmacology Wiley

GABAB receptor isoforms GBR1a and GBR1b, appear to be associated with pre‐ and post‐synaptic elements respectively in rat and human cerebellum

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Publisher
Wiley
Copyright
"Copyright © 1999 Wiley Subscription Services, Inc., A Wiley Company"
ISSN
0007-1188
eISSN
1476-5381
DOI
10.1038/sj.bjp.0702460
pmid
10217533
Publisher site
See Article on Publisher Site

Abstract

Metabotropic γ‐aminobutyric acid (GABA) receptors, GABAB, are coupled through G‐proteins to K+ and Ca2+ channels in neuronal membranes. Cloning of the GABAB receptor has not uncovered receptor subtypes, but demonstrated two isoforms, designated GBR1a and GBR1b, which differ in their N terminal regions. In the rodent cerebellum GABAB receptors are localized to a greater extent in the molecular layer, and are reported to exist on granule cell parallel fibre terminals and Purkinje cell (PC) dendrites, which may represent pre‐ and post‐synaptic receptors. The objective of this study was to localize the mRNA splice variants, GBR1a and GBR1b for GABAB receptors in rat cerebellum, for comparison with the localization in human cerebellum using in situ hybridization. Receptor autoradiography was performed utilizing [3H]‐CGP62349 to localize GABAB receptors in rat and human cerebellum. Radioactively labelled oligonucleotide probes were used to localize GBR1a and GBR1b, and by dipping slides in photographic emulsion, silver grain images were obtained for quantification at the cellular level. Binding of 0.5 nM [3H]‐CGP62349 demonstrated significantly higher binding to GABAB receptors in the molecular layer than the granule cell (GC) layer of rat cerebellum (molecular layer binding 200±11% of GC layer; P<0.0001). GBR1a mRNA expression was found to be predominantly in the GC layer (PC layer grains 6±6% of GC layer grains; P<0.05), and GBR1b expression predominantly in PCs (PC layer grains 818±14% of GC layer grains; P<0.0001). The differential distribution of GBR1a and GBR1b mRNA splice variants for GABAB receptors suggests a possible association of GBR1a and GBR1b with pre‐ and post‐synaptic elements respectively.

Journal

British Journal of PharmacologyWiley

Published: Mar 1, 1999

Keywords: ; ; ; ; ;

References

  • GABAB receptors: drugs meet clones
    BETTLER, B.; KAUPMANN, K.; BOWERY, N.G.
  • Pharmacologically distinct GABAB receptors that mediate inhibition of GABA and glutamate release in human neocortex
    BONANNO, G.; FASSIO, A.; SCHMID, G.; SEVERI, P.; SALA, R.; RAITERI, M.

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