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Molecular and Electrophysiological Evidence for a GABAC Receptor in Thyrotropin-Secreting Cells

2000; Oxford University Press; Volume: 141; Issue: 5 Linguagem: Inglês

10.1210/en.141.5.1627

1945-7170

Éric Boué‐Grabot,

Neuroscience and Neuropharmacology Research

In the pituitary, GABA regulates the release of several hormones via different receptors. GABAC receptors are heterooligomers that differ from GABAA receptors in that they containρ -subunits and are insensitive to bicuculline. However, molecular and functional evidence for the presence of GABAC receptors outside the retina has yet to be established. The present work was performed on guinea pig and rat pituitaries. Both Northern blot and RT-PCR analysis showed that, although ρ1- and ρ2-subunits were expressed at similar levels in the rat retina, ρ1 messenger RNA (mRNA) was enriched, relative to ρ2 mRNA in the rat pituitary. Northern blot experiments also showed that, in the pituitary, ρ1 andρ 2 mRNAs are shorter in size than those expressed in the retina. The use of a subunit-specific antibody revealed colocalization ofρ 1-subunit and anti-TSH labeling on rat pituitary sections. TSH guinea pig pituitary cells were also labeled with a ρ-subunit antiserum. Moreover, whole-cell patch clamp on single guinea pig TSH cells showed that GABA induced a bicuculline- insensitive Cl− current. In contrast to the Cl− current generated by GABAC receptors in the retina, the bicuculline-insensitive Cl− currents in TSH cells quickly desensitized. These results suggest that a novel GABAC receptor may regulate TSH secretion and that the structure and/or biochemical regulation of this pituitary receptor is different from that found in the retina.