Postnatal ontogeny of GABAB binding in rat brain

doi:10.1016/0306-4522(94)90392-1

Neuroscience

Volume 62, Issue 2, September 1994, Pages 601-613

https://doi.org/10.1016/0306-4522(94)90392-1 Get rights and content

Abstract

The postnatal development of GABA_B binding sites in rat brain was studied by quantitative receptor autoradiography using [³H]GABA under selective conditions. Binding levels peak at regionally specific times during the first three weeks of life and then decline to adult levels. GABA_B binding peaked in the globus pallidus, vestibular and spinal trigeminal nuclei, and the CA3 region of the hippocampus at postnatal day 3; in the striatum, nucleus accumbens, inferior olive, septum, dentate gyrus and CA1 region of the hippocampus at postnatal day 7; in the neocortex and thalamus at postnatal day 14; and in the medial geniculate at postnatal day 21. Following these regionally specific peaks, binding decreased to postnatal day 28 levels. Further significant decreases in binding were observed in all regions examined between postnatal day 28 and adulthood. Comparisons of binding site pharmacology reveal equipotent displacement of GABA_B binding by several competitive agonists and antagonists in postnatal day 7 and adult rat brain, indicating that immature and adult binding sites have similar pharmacological properties with regard to these compounds. The GABA_B receptor antagonist CGP 54626A, however, inhibited binding more potently in the postnatal day 7 thalamus and neocortex than in these areas in the adult brain. The guanyl nucleotide analogue guanosine 5'-O-(3-thiotriphasphate) inhibited GABA_B binding extensively in both postnatal day 7 and adult brain. The non-competitive antagonist zinc also inhibited GABA_B binding at both ages and was more potent in postnatal day 7 brain than in adult brain. Saturation analyses reveal two binding sites with similar affinities in both immature and adult rat brain, indicating that postnatal modulation of GABA_B binding reflects changes in binding site density rather than modulation of binding site affinity. While immature GABA_B binding sites share most pharmacological characteristics with adult binding sites and appear to be coupled to G-proteins at an early age, their interactions with zinc and CGP 54626A suggest that GABA_B binding sites in immature brain may have a distinct pharmacological profile.

Our data suggest significant regional and pharmacological changes in GABA_B binding during development. The implications of these findings are discussed with regards to a possible role of GABA_B receptors in the development of the central nervous system.

Reference (73)

AsanoT. et al.
Prevention of the agonist binding to γ-aminobutyric acid B receptors by guanine nucleotides and islet-activating protein, pertussis toxin, in bovine cerebral cortex
J. biol. Chem.
(1985)
AsanumaC. et al.
Observations on the development of certain ascending inputs to the thalamus in rats. I. Postnatal development
Devl Brain Res.
(1988)
BalcarV.J. et al.
Is there a non-synaptic component in the K⁺-stimulated release of GABA in the developing rat cortex?
Devl Brain Res.
(1983)
BeckerC.-M. et al.
Expression of inhibitory glycine receptors in postnatal rat cerebral cortex
Brain Res.
(1993)
BormannJ.
Electrophysiology of GABA_A and GABA_B receptor subtypes
Trends Neurosci.
(1988)
CherubiniE. et al.
GABA mediated excitation in immature rat CA3 hippocampal neurons
Int. J. devl Neurosci.
(1990)
ChuD.C.M. et al.
Distribution and kinetics of GABA_B binding sites in rat central nervous system: a quantitative autoradioraphic study
Neuroscience
(1990)
CoyleJ.T. et al.
Neurochemical aspects of the ontogenesis of GABAergic neurons in the rat brain
Brain Res.
(1976)
DavalJ.-L. et al.
Quantitative autoradiographic study of the postnatal development of benzodiazepine binding sites and their coupling to GABA receptors in the rat brain
Int. J. devl Neurosci.
(1991)
GarantD. et al.
The density of GABA_B binding sites in the substantia nigra is greater in rat pups than in adults
Ear. J. Pharmac.
(1992)

GreenamyreJ.T. et al.

Regional ontogeny of a unique glutamate recognition site in rat brain: an autoradiographic study

Int. J. devl Neurosci.

(1990)

HansenG.H. et al.

GABA influences the ultrastructure composition of cerebellar granule cells during development in culture

Int. J. devl Neurosci.

(1984)

HappeH.K. et al.

Tritium quench in autoradiography during postnatal development of rat forebrain

Brain Res.

(1990)

InselT.R. et al.

The ontogeny of excitatory amino acid receptors in the rat forebrain—I. N-Methyl-d-aspartate and quisqualate receptors

Neuroscience

(1990)

JanigroD. et al.

Effects of GABA and baclofen on pyramidal cells in the developing rabbit hippocampus: an ‘in vitro’ study

Devl Brain Res.

(1988)

MadtesP. et al.

GABA as a trophic factor during development

Life Sci.

(1983)

McDonaldJ.W. et al.

Differential ontogenic development of three receptors comprising the NMDA receptor/channel complex in the rat hippocampus

Ex.pl Neurol.

(1990)

McLaughlinB.J. et al.

The fine structural localization of glutamate decarboxylase in developing axonal processes and presynaptic terminals of rodent cerebellum

Brain Res.

(1975)

MichlerA.

Involvement of GABA receptors in the reculation of neurite growth in cultured embryonic chick tectum

Int. J. devl Neurosci.

(1990)

MillerL.P. et al.

The ontogeny of excitatory amino acid receptors in the rat forebrain—II. Kainic acid receptors

Neuroscience

(1990)

MonyerH. et al.

Glutamate-operated channels: developmentally early and mature forms arise by alternative splicing

Neuron

(1991)

OlpeH.-R. et al.

The actions of orally active GABA_B receptor antagonists on GABAergic transmission in vivo and in vitro

Eur. J. Pharmac.

(1993)

ParduczA. et al.

Fine structural changes in the superior cervical ganglion of adult rats after long-term administration of baclofen, a GABA_B receptor agonist

Neuroscience

(1990)

RedburnD.A. et al.

Development of rat brain uptake and calcium-dependent release of GABA

Brain Res.

(1978)

ScheibelM.E. et al.

Ontogenic development of somatosensory thalamus. I. Morphogenesis

Expl Neurol.

(1976)

SchererR.W et al.

Evidence for pharmacologically distinct subsets of GABA_B receptors

Brain Res.

(1988)

SeressL. et al.

Te development of GABAergic neurons in the real hippocampal formation. An immunocytochemical study

Devl Brain Res.

(1988)

SuzdakP.D. et al.

Effect of chronic imiprimine or baclofen on GABA-B binding and cyclic AMP production in cerebral cortex

Eur. J. Pharmac.

(1986)

SwannJ.W. et al.

Postnatal development of [³H]-mediated synaptic inhibition in rat hippocampus

Neuroscience

(1989)

TremblayE. et al.

Transient increased density of NMDA binding sites in the developing rat hippocampus

Brain Res.

(1988)

TurgeonS.M. et al.

Zinc modulates GABA_B binding in rat brain

Brain Res.

(1992)

TurgeonS.M. et al.

Pharmacology, distribution, cellular localization, and development of GABA_B binding in rodent cerebellum

Neuroscience

(1993)

WolffJ.R. et al.

Development of GABAergic neurons in rat visual cortex as identified by glutamate decarboxylase-like immunoreactivity

Neurosci. Lett.

(1984)

XiaY. et al.

Ontogeny and distribution of GABA_B receptors in rat brainstem and rostral brain areas

Neuroscience

(1992)

Al-DahanM.I. et al.

Effect of guanosine 5'-O-(3-thiotriphosphate) and calcium on γ-aminobutyric acid_B binding as a function of postnatal development

J. Neurochem.

(1989)

AldinoA.C et al.

Ontogenic development of GABA recognition sites in different brain areas

Pharmac. Res. Commun.

(1980)

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Postnatal ontogeny of GABAB binding in rat brain

Abstract

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Ex.pl Neurol.

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Int. J. devl Neurosci.

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Eur. J. Pharmac.

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Expl Neurol.

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Devl Brain Res.

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Brain Res.

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Effect of guanosine 5'-O-(3-thiotriphosphate) and calcium on γ-aminobutyric acidB binding as a function of postnatal development

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Postnatal ontogeny of GABA_B binding in rat brain

Effect of guanosine 5'-O-(3-thiotriphosphate) and calcium on γ-aminobutyric acid_B binding as a function of postnatal development