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J. Biol. Chem., Vol. 278, Issue 22, 20192-20195, May 30, 2003

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Molecular and Physiological Evidence for Functional -Aminobutyric Acid (GABA)-C Receptors in Growth Hormone-secreting Cells^*

Katia Gamel-Didelon , Lars Kunz , Karl Josef Föhr , Manfred Gratzl  and Artur Mayerhofer  ¶

From the Anatomisches Institut der Universität München, 80802 München, Germany and the Klinik für Anästhesiologie, Universität Ulm, 89070 Ulm, Germany

The neurotransmitter -aminobutyric acid (GABA), released by hypothalamic neurons as well as by growth hormone- (GH) and adrenocorticotropin-producing cells, is a regulator of pituitary endocrine functions. Different classes of GABA receptors may be involved. In this study, we report that GH cells, isolated by laser microdissection from rat pituitary slices, possess the GABA-C receptor subunit ₂. We also demonstrate that in the GH adenoma cell line, GH3, GABA-C receptor subunits are not only expressed but also form functional channels. GABA-induced Cl^- currents were recorded using the whole cell patch clamp technique; these currents were insensitive to bicuculline (a GABA-A antagonist) but could be induced by the GABA-C agonist cis-4-aminocrotonic acid. In contrast to typical GABA-C mediated currents in neurons, they quickly desensitized. Ca²⁺_i recordings were also performed on GH3 cells. The application of either GABA or cis-4-aminocrotonic acid led to Ca²⁺ transients of similar amplitude, indicating that the activation of GABA-C receptors in GH3 cells may cause membrane depolarization, opening of voltage-gated Ca²⁺ channels, and a subsequent Ca²⁺ influx. Our results point at a role for GABA in pituitary GH cells and disclose an additional pathway to the one known via GABA-B receptors.

Received for publication, February 19, 2003 , and in revised form, March 25, 2003.

^* This work was supported by a grant from Eli Lilly International Foundation. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^¶ To whom correspondence should be addressed: Anatomisches Institut der Universität München, Biedersteiner Strasse 29, 80802 München, Germany. Tel.: 49-89-4140-3150; Fax: 49-89-397035; E-mail: Mayerhofer{at}lrz.uni-muenchen.de.

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