Molecular, pharmacological and functional properties of GABAA receptors in anterior pituitary cells
Anterior pituitary cells express γ-aminobutyric acid (GABA)-A receptor-channels, but their structure, distribution within the secretory cell types, and nature of action have not been clarified. Here we addressed these questions using cultured anterior pituitary cells from postpubertal female rats a...
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Published in | The Journal of physiology Vol. 586; no. 13; pp. 3097 - 3111 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford, UK
The Physiological Society
01.07.2008
Blackwell Publishing Ltd Blackwell Science Inc |
Subjects | |
Online Access | Get full text |
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Summary: | Anterior pituitary cells express γ-aminobutyric acid (GABA)-A receptor-channels, but their structure, distribution within
the secretory cell types, and nature of action have not been clarified. Here we addressed these questions using cultured anterior
pituitary cells from postpubertal female rats and immortalized αT3-1 and GH 3 cells. Our results show that mRNAs for all GABA A receptor subunits are expressed in pituitary cells and that α1/β1 subunit proteins are present in all secretory cells. In
voltage-clamped gramicidin-perforated cells, GABA induced dose-dependent increases in current amplitude that were inhibited
by bicuculline and picrotoxin and facilitated by diazepam and zolpidem in a concentration-dependent manner. In intact cells,
GABA and the GABA A receptor agonist muscimol caused a rapid and transient increase in intracellular calcium, whereas the GABA B receptor agonist baclofen was ineffective, suggesting that chloride-mediated depolarization activates voltage-gated calcium
channels. Consistent with this finding, RT-PCR analysis indicated high expression of NKCC1, but not KCC2 cation/chloride transporter
mRNAs in pituitary cells. Furthermore, the GABA A channel reversal potential for chloride ions was positive to the baseline membrane potential in most cells and the activation
of ion channels by GABA resulted in depolarization of cells and modulation of spontaneous electrical activity. These results
indicate that secretory pituitary cells express functional GABA A receptor-channels that are depolarizing. |
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Bibliography: | I. Bjelobaba: Institute for Biological Research “Sinisa Stankovic”, 11000 Belgrade, Serbia. Authors' present addresses H. Zemkova: Institute of Physiology, Academy of Sciences of the Czech Republic, 142 20 Prague 4, Czech Republic. |
ISSN: | 0022-3751 1469-7793 |
DOI: | 10.1113/jphysiol.2008.153148 |