GABA signaling and neuroactive steroids in adrenal medullary chromaffin cells

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, but not synaptic-like microvesicles. The...

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Main Authors: Keita eHarada, Hidetada eMatsuoka, Hiroaki eFujiwara, Yoichi eUeta, Yuchio eYanagawa, Masumi eInoue
Format: Article
Language:English
Published: Frontiers Media S.A. 2016-04-01
Series:Frontiers in Cellular Neuroscience
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fncel.2016.00100/full
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author Keita eHarada
Hidetada eMatsuoka
Hiroaki eFujiwara
Yoichi eUeta
Yuchio eYanagawa
Masumi eInoue
author_facet Keita eHarada
Hidetada eMatsuoka
Hiroaki eFujiwara
Yoichi eUeta
Yuchio eYanagawa
Masumi eInoue
author_sort Keita eHarada
collection DOAJ
description 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, but not synaptic-like microvesicles. The 32/32 complex represents the majority of GABAA receptors expressed in rat and guinea pig chromaffin cells, whereas PC12 cells, an immortalized rat chromaffin cell line, express the 1 subunit as well as the 3. The expression of 3, but not 1, in PC12 cells is enhanced by glucocorticoid activity, which may be mediated by both the mineralocorticoid receptor and the glucocorticoid receptor. GABA has two actions mediated by GABAA 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 GABAA 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 GABAA receptors and the lack of expression of plasma membrane GABA transporters. 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.
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spelling doaj.art-733b89180e3548af89cb613eb23b0e142022-12-21T23:23:02ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022016-04-011010.3389/fncel.2016.00100155038GABA signaling and neuroactive steroids in adrenal medullary chromaffin cellsKeita eHarada0Hidetada eMatsuoka1Hiroaki eFujiwara2Yoichi eUeta3Yuchio eYanagawa4Masumi eInoue5University of Occupational and Environmental Health School of MedicineUniversity of Occupational and Environmental Health School of MedicineUniversity of Occupational and Environmental Health School of MedicineUniversity of Occupational and Environmental Health School of MedicineUniversity of Occupational and Environmental Health School of MedicineUniversity of Occupational and Environmental Health School of MedicineGABA 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, but not synaptic-like microvesicles. The 32/32 complex represents the majority of GABAA receptors expressed in rat and guinea pig chromaffin cells, whereas PC12 cells, an immortalized rat chromaffin cell line, express the 1 subunit as well as the 3. The expression of 3, but not 1, in PC12 cells is enhanced by glucocorticoid activity, which may be mediated by both the mineralocorticoid receptor and the glucocorticoid receptor. GABA has two actions mediated by GABAA 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 GABAA 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 GABAA receptors and the lack of expression of plasma membrane GABA transporters. 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.http://journal.frontiersin.org/Journal/10.3389/fncel.2016.00100/fullGABAGABAA receptorsGAD67paracrineneuroactive steroidPC12 cell
spellingShingle Keita eHarada
Hidetada eMatsuoka
Hiroaki eFujiwara
Yoichi eUeta
Yuchio eYanagawa
Masumi eInoue
GABA signaling and neuroactive steroids in adrenal medullary chromaffin cells
Frontiers in Cellular Neuroscience
GABA
GABAA receptors
GAD67
paracrine
neuroactive steroid
PC12 cell
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 GABA
GABAA receptors
GAD67
paracrine
neuroactive steroid
PC12 cell
url http://journal.frontiersin.org/Journal/10.3389/fncel.2016.00100/full
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