What question did this study set out to answer?

To characterize the coupling of cerebral GABAB receptors to distinct G protein subtypes and determine how positive allosteric modulators influence this coupling.

November 16, 2007Journal of Neurochemistry

Influence of positive allosteric modulators on GABABreceptor coupling in rat brain: a scintillation proximity assay characterisation of G protein subtypes

View Full Paper

Ask AI

Bookmark

Authors

CCClotilde Mannoury la CourServier (France)CHChloé HerbellesAVL (France)VPValérie PasteauServier (France)

Discussion

Member takes

Implication

Laboratory study demonstrates that positive allosteric modulators preferentially boost GABAB receptor coupling to Galphao in rat brain, indicating subtype-selective signaling mechanisms.

Key Points

To characterize the coupling of cerebral GABAB receptors to distinct G protein subtypes and determine how positive allosteric modulators influence this coupling.
Measured [(35)S]GTPgammaS binding across rat cerebral cortex, hippocampus, and cerebellum using an antibody-capture scintillation proximity assay.
Evaluated responses to GABA, (R)-baclofen, and SKF97581 in the presence or absence of positive allosteric modulators (GS39783, CGP7930, CGP13501) and the antagonist CGP55845A.
Assessed G protein coupling in human embryonic kidney cells expressing GABAB(1a+2) or GABAB(1b+2) receptor heterodimers.
GABA and agonists concentration-dependently stimulated [(35)S]GTPgammaS binding to Galphao and, less robustly, Galphai(1/3) in cortex, hippocampus, and cerebellum, while Gq and Gs/olf remained unaffected.
Positive allosteric modulators selectively enhanced the efficacy and potency of agonist-induced coupling to Galphao across brain regions, but failed to alter efficacy at Galphai(1/3).
In recombinant human embryonic kidney cells, allosteric modulators increased the potency of GABA at Galphai(1/3) without detectably altering its maximal efficacy.

Cite This Study

Cour et al. (2007) studied this question.

synapsesocial.com/papers/6a70bbfba2d7cf2e39c2b516 https://doi.org/10.1111/j.1471-4159.2007.05131.x

View Full Paper

Ask AI

Bookmark

Implication

Laboratory study demonstrates that positive allosteric modulators preferentially boost GABAB receptor coupling to Galphao in rat brain, indicating subtype-selective signaling mechanisms.

Influence of positive allosteric modulators on GABABreceptor coupling in rat brain: a scintillation proximity assay characterisation of G protein subtypes

Discussion

Member takes

Implication

Key Points

Cite This Study

Influence of positive allosteric modulators on GABABreceptor coupling in rat brain: a scintillation proximity assay characterisation of G protein subtypes

Discussion

Member takes

Implication

Key Points

Cite This Study

Also Consider

Also Consider