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GABA Receptor Expression
Published by Anonymous on 2007/9/30 (1646 reads)
1: Eur J Pharmacol. 2004 Oct 1;500(1-3):413-25.


Modulation of GABA(A) receptor gene expression by allopregnanolone and ethanol.

Follesa P, Biggio F, Caria S, Gorini G, Biggio G.

Department of Experimental Biology, Section of Neuroscience, and Center of Excellence for the Neurobiology of Dependence, University of Cagliari, 09123 Cagliari, Italy.

Expression of specific gamma-aminobutyric acid type A (GABA(A)) receptor subunit genes in neurons is affected by endogenous modulators of receptor function such as neuroactive steroids. This effect of steroids appears to be mediated through modulation of GABA(A) receptor signalling mechanisms that control the expression of specific receptor subunit genes. Furthermore, the specific outcomes of such signalling appear to differ among neurons in different regions of the brain. Neuroactive steroids such as the progesterone metabolite allopregnanolone might thus exert differential effects on GABA(A) receptor plasticity in distinct neuronal cell populations, likely accounting for some of the physiological actions of these compounds. Here we summarise experimental data obtained both in vivo and in vitro that show how fluctuations in the concentration of allopregnanolone regulate both the expression and function of GABA(A) receptors and consequently affect behaviour. Such regulation is operative both during physiological conditions such as pregnancy and lactation as well as in pharmacologically induced states such as pseudopregnancy and long-term treatment with steroid derivatives or anxiolytic-hypnotic drugs. Accordingly, long-lasting exposure of GABA(A) receptors to ethanol, as well as its withdrawal, induces marked effects on receptor structure and function. These results suggest the possible synergic action between endogenous steroids and ethanol in modulating the functional activity of specific neuronal populations.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 15464049 [PubMed - indexed for MEDLINE]

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2: Neurochem Int. 2000 Nov-Dec;37(5-6):453-61.


Regional variations in the effects of chronic ethanol administration on GABA(A) receptor expression: potential mechanisms.

Grobin AC, Papadeas ST, Morrow AL.

Skipper Bowles Center for Alcohol Studies, Department of Psychiatry, University of North Carolina at Chapel Hill, USA.

Gamma-aminobutyric acid type A (GABA(A)) receptors in brain adapt to chronic ethanol exposure via changes in receptor function and subunit expression. The present review summarizes currently available data regarding changes in GABA(A) receptor subunit mRNA and peptide expression. Data are presented from various different brain regions and the variations between specific brain regions used to draw conclusions about mechanisms that may underlie GABA(A) receptor adaptations during chronic ethanol exposure. In the whole cerebral cortex, chronic ethanol exposure leads to a reduction of GABA(A) receptor alpha1 subunit mRNA and peptide levels and a near equivalent increase in alpha4 subunit mRNA and peptide levels. This observation is the primary support for the hypothesis that altered receptor composition is a mechanism for GABA(A) receptor adaptation produced by chronic ethanol exposure. However, other brain regions do not display similar patterns of subunit changes. Moreover, subregions within cortex (prefrontal, cingulate, parietal, motor, and piriform) exhibit patterns of changes in subunit expression that differ from whole cortex. Therefore, regional differences in GABA(A) receptor subunit expression are evident following chronic ethanol administration, thus suggesting that multiple mechanisms contribute to the regulation of GABA(A) receptor expression. These mechanisms may include the involvement of other neurotransmitter systems, endogenous steroids and second or third messenger cross-talk.

Publication Types:
Review

PMID: 10871697 [PubMed - indexed for MEDLINE]

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3: Eur J Pharmacol. 1998 Jul 3;352(1):1-14.


Pharmacological and functional implications of developmentally-regulated changes in GABA(A) receptor subunit expression in the cerebellum.

Carlson BX, Elster L, Schousboe A.

PharmaBiotec Research Center, Dept. of Pharmacology, The Royal Danish School of Pharmacy, Copenhagen.

The cerebellum undergoes many morphological, pharmacological, and electrophysiological changes during the first 3 weeks of postnatal development. The purpose of this review is to present the most up to date synopsis of the pharmacological and functional changes in, gamma-aminobutyric acid (GABA) type A receptors during this time of cerebellar maturation. Since most of the diversity in cerebellar, GABA(A) receptor pharmacology lies within the granule cell layer, research groups have focused on this area of the cerebellum to study the developmental changes in GABA(A) receptor subunit expression and the neurodifferentiating factors involved in regulating this expression. Thus, it is important to note that developmental changes in GABA(A) receptor composition and its corresponding pharmacology will be essential for determining the type of GABA-mediated transmission that occurs between neuronal contacts in the neonatal and subsequently in the mature cerebellum.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 9718261 [PubMed - indexed for MEDLINE]

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4: J Neurosci Res. 1995 May 1;41(1):1-7.


Modulatory actions of gamma aminobutyric acid (GABA) on GABA type A receptor subunit expression and function.

Schousboe A, Redburn DA.

Department of Biological Sciences, Royal Danish School of Pharmacy, Copenhagen.

Gamma aminobutyric acid (GABA) is present in the central nervous system (CNS) during very early embryogenesis. It is therefore likely to play a role not only as a neurotransmitter but also as a signal molecule for neuronal differentiation, growth, and development. It has been firmly established that formation of synapses is strengthened by GABA, and the expression of certain subunits of the GABA type A (GABAA) receptor complex is clearly promoted by GABA. This latter effect of GABA may have profound implications for the functional activity of GABAergic synapses since the pharmacological properties of GABAA receptors are governed by the subunit composition of the receptor complex. Dynamic changes in GABAA receptor expression and diversity during development and differentiation may therefore play important roles for the inhibitory potential of the CNS during mature stages.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 7674371 [PubMed - indexed for MEDLINE]

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5: Adv Biochem Psychopharmacol. 1992;47:81-5.


Selective expression of the mRNA encoding the short isoform of the gamma 2 GABA-A receptor subunit in rat pituitary cells.

Valerio A, Spano PF, Memo M.

Department of Biomedical Sciences and Biotechnology, University of Brescia, Italy.

Publication Types:
Review

PMID: 1324590 [PubMed - indexed for MEDLINE]
 

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