This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Metzeler, K. Articles by Gratzl, M. Search for Related Content PubMed PubMed Citation Articles by Metzeler, K. Articles by Gratzl, M.

An Intrinsic -Aminobutyric Acid (GABA)ergic System in the Adrenal Cortex: Findings from Human and Rat Adrenal Glands and the NCI-H295R Cell Line

Anatomisches Institut, Universität München, 80802 München, Germany

Address all correspondence and requests for reprints to: Dr. Manfred Gratzl, Anatomisches Institut der Universität München, Biedersteiner Strasse 29, 80802 München, Germany. E-mail: gratzl{at}LMU.de.

-Aminobutyric acid (GABA), a major neurotransmitter in the central nervous system, also acts as a paracrine or autocrine signaling molecule in endocrine tissues such as the pancreatic islets, adenohypophysis, and testis. In the present study, we describe local GABA production and functional GABA_B receptors in the adrenal cortex, possibly forming an auto- or paracrine GABAergic system. Using immunohistochemistry and RT-PCR, we localized the GABA-synthesizing enzyme glutamate decarboxylase 67 and the vesicular GABA transporter in steroid-producing cells of the human and rat adrenal cortex. Immunocytochemistry, Western blots, and RT-PCR experiments demonstrated the presence of glutamate decarboxylase 67 in the human adrenocortical cell line NCI-H295R. Measurements of glutamate decarboxylase activity confirmed that, in these cells and in rat adrenals, glutamate is decarboxylated to form GABA. In addition, we found expression of the GABA_B(1a), GABA_B(1e), and GABA_B(2) subunits of the heterodimeric GABA_B receptor in NCI-H295R cells as shown by RT-PCR. GABA_B(1a) and its truncated splice variant GABA_B(1e) were also found in human and rat adrenal glands. Immunostaining for the GABA_B(2) subunit revealed its presence in the human and rat adrenal cortex and in NCI-H295R cells. The GABA_B receptors we identified were functional because the GABA_B agonist baclofen inhibited T-type Ca²⁺ currents in whole-cell patch clamp experiments on NCI-H295R cells. This effect was blocked by pertussis toxin. Furthermore, the ₂-, ₃-, ß₂-, ß₃- ₂-, and -subunits of the GABA_A receptor were detected in this cell line by RT-PCR. Hence, we conclude that GABA is synthesized and stored by steroid-producing cells of the adrenal cortex and may influence these cells in a paracrine or autocrine manner.

This article has been cited by other articles:

				H. Matsuoka, K. Harada, Y. Endo, A. Warashina, Y. Doi, J. Nakamura, and M. Inoue Molecular mechanisms supporting a paracrine role of GABA in rat adrenal medullary cells J. Physiol., October 15, 2008; 586(20): 4825 - 4842. [Abstract] [Full Text] [PDF]

				Y. Osawa, D. Xu, D. Sternberg, J. R. Sonett, J. D'Armiento, R. A. Panettieri, and C. W. Emala Functional expression of the GABAB receptor in human airway smooth muscle Am J Physiol Lung Cell Mol Physiol, November 1, 2006; 291(5): L923 - L931. [Abstract] [Full Text] [PDF]