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Molecular, pharmacological and functional properties of GABA A receptors in anterior pituitary cells
Author(s) -
Zemkova Hana W.,
Bjelobaba Ivana,
Tomic Melanija,
Zemkova Hana,
Stojilkovic Stanko S.
Publication year - 2008
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2008.153148
Subject(s) - muscimol , depolarization , gabaa receptor , chloride channel , medicine , endocrinology , bicuculline , chemistry , agonist , gaba receptor , receptor , gabaergic , anterior pituitary , membrane potential , picrotoxin , gamma aminobutyric acid , microbiology and biotechnology , biophysics , biology , biochemistry , hormone
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.