Cargando…
GABA Signaling and Neuroactive Steroids in Adrenal Medullary Chromaffin Cells
Gamma-aminobutyric acid (GABA) is produced not only in the brain, but also in endocrine cells by the two isoforms of glutamic acid decarboxylase (GAD), GAD65 and GAD67. In rat adrenal medullary chromaffin cells only GAD67 is expressed, and GABA is stored in large dense core vesicles (LDCVs), but not...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4834308/ https://www.ncbi.nlm.nih.gov/pubmed/27147972 http://dx.doi.org/10.3389/fncel.2016.00100 |
_version_ | 1782427465602301952 |
---|---|
author | Harada, Keita Matsuoka, Hidetada Fujihara, Hiroaki Ueta, Yoichi Yanagawa, Yuchio Inoue, Masumi |
author_facet | Harada, Keita Matsuoka, Hidetada Fujihara, Hiroaki Ueta, Yoichi Yanagawa, Yuchio Inoue, Masumi |
author_sort | Harada, Keita |
collection | PubMed |
description | Gamma-aminobutyric acid (GABA) is produced not only in the brain, but also in endocrine cells by the two isoforms of glutamic acid decarboxylase (GAD), GAD65 and GAD67. In rat adrenal medullary chromaffin cells only GAD67 is expressed, and GABA is stored in large dense core vesicles (LDCVs), but not synaptic-like microvesicles (SLMVs). The α3β2/3γ2 complex represents the majority of GABA(A) receptors expressed in rat and guinea pig chromaffin cells, whereas PC12 cells, an immortalized rat chromaffin cell line, express the α1 subunit as well as the α3. The expression of α3, but not α1, in PC12 cells is enhanced by glucocorticoid activity, which may be mediated by both the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR). GABA has two actions mediated by GABA(A) receptors in chromaffin cells: it induces catecholamine secretion by itself and produces an inhibition of synaptically evoked secretion by a shunt effect. Allopregnanolone, a neuroactive steroid which is secreted from the adrenal cortex, produces a marked facilitation of GABA(A) receptor channel activity. Since there are no GABAergic nerve fibers in the adrenal medulla, GABA may function as a para/autocrine factor in the chromaffin cells. This function of GABA may be facilitated by expression of the immature isoforms of GAD and GABA(A) receptors and the lack of expression of plasma membrane GABA transporters (GATs). In this review, we will consider how the para/autocrine function of GABA is achieved, focusing on the structural and molecular mechanisms for GABA signaling. |
format | Online Article Text |
id | pubmed-4834308 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-48343082016-05-04 GABA Signaling and Neuroactive Steroids in Adrenal Medullary Chromaffin Cells Harada, Keita Matsuoka, Hidetada Fujihara, Hiroaki Ueta, Yoichi Yanagawa, Yuchio Inoue, Masumi Front Cell Neurosci Neuroscience Gamma-aminobutyric acid (GABA) is produced not only in the brain, but also in endocrine cells by the two isoforms of glutamic acid decarboxylase (GAD), GAD65 and GAD67. In rat adrenal medullary chromaffin cells only GAD67 is expressed, and GABA is stored in large dense core vesicles (LDCVs), but not synaptic-like microvesicles (SLMVs). The α3β2/3γ2 complex represents the majority of GABA(A) receptors expressed in rat and guinea pig chromaffin cells, whereas PC12 cells, an immortalized rat chromaffin cell line, express the α1 subunit as well as the α3. The expression of α3, but not α1, in PC12 cells is enhanced by glucocorticoid activity, which may be mediated by both the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR). GABA has two actions mediated by GABA(A) receptors in chromaffin cells: it induces catecholamine secretion by itself and produces an inhibition of synaptically evoked secretion by a shunt effect. Allopregnanolone, a neuroactive steroid which is secreted from the adrenal cortex, produces a marked facilitation of GABA(A) receptor channel activity. Since there are no GABAergic nerve fibers in the adrenal medulla, GABA may function as a para/autocrine factor in the chromaffin cells. This function of GABA may be facilitated by expression of the immature isoforms of GAD and GABA(A) receptors and the lack of expression of plasma membrane GABA transporters (GATs). In this review, we will consider how the para/autocrine function of GABA is achieved, focusing on the structural and molecular mechanisms for GABA signaling. Frontiers Media S.A. 2016-04-18 /pmc/articles/PMC4834308/ /pubmed/27147972 http://dx.doi.org/10.3389/fncel.2016.00100 Text en Copyright © 2016 Harada, Matsuoka, Fujihara, Ueta, Yanagawa and Inoue. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution and reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Harada, Keita Matsuoka, Hidetada Fujihara, Hiroaki Ueta, Yoichi Yanagawa, Yuchio Inoue, Masumi GABA Signaling and Neuroactive Steroids in Adrenal Medullary Chromaffin Cells |
title | GABA Signaling and Neuroactive Steroids in Adrenal Medullary Chromaffin Cells |
title_full | GABA Signaling and Neuroactive Steroids in Adrenal Medullary Chromaffin Cells |
title_fullStr | GABA Signaling and Neuroactive Steroids in Adrenal Medullary Chromaffin Cells |
title_full_unstemmed | GABA Signaling and Neuroactive Steroids in Adrenal Medullary Chromaffin Cells |
title_short | GABA Signaling and Neuroactive Steroids in Adrenal Medullary Chromaffin Cells |
title_sort | gaba signaling and neuroactive steroids in adrenal medullary chromaffin cells |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4834308/ https://www.ncbi.nlm.nih.gov/pubmed/27147972 http://dx.doi.org/10.3389/fncel.2016.00100 |
work_keys_str_mv | AT haradakeita gabasignalingandneuroactivesteroidsinadrenalmedullarychromaffincells AT matsuokahidetada gabasignalingandneuroactivesteroidsinadrenalmedullarychromaffincells AT fujiharahiroaki gabasignalingandneuroactivesteroidsinadrenalmedullarychromaffincells AT uetayoichi gabasignalingandneuroactivesteroidsinadrenalmedullarychromaffincells AT yanagawayuchio gabasignalingandneuroactivesteroidsinadrenalmedullarychromaffincells AT inouemasumi gabasignalingandneuroactivesteroidsinadrenalmedullarychromaffincells |