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GABA Signaling and Neuroactive Steroids in Adrenal Medullary Chromaffin Cells.

Harada K, Matsuoka H, Fujihara H, Ueta Y, Yanagawa Y, Inoue M - Front Cell Neurosci (2016)

Bottom Line: 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.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 (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.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell and Systems Physiology, University of Occupational and Environmental Health School of Medicine Kitakyushu, Japan.

ABSTRACT
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 GABAA 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 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 (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.

No MeSH data available.


Related in: MedlinePlus

Summary of effects of adrenal cortical hormones on GABA signaling. The left image represents hematoxylin-eosin staining of mouse adrenal gland. GABA is stored in large dense core vesicles (LDCVs) or chromaffin granules in chromaffn cells. Glucocorticoids produce an increase in expression of α3-containing GABAA receptors whereas allopregnanolone produces facilitation of GABAA receptor Cl− channel activity.
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Figure 6: Summary of effects of adrenal cortical hormones on GABA signaling. The left image represents hematoxylin-eosin staining of mouse adrenal gland. GABA is stored in large dense core vesicles (LDCVs) or chromaffin granules in chromaffn cells. Glucocorticoids produce an increase in expression of α3-containing GABAA receptors whereas allopregnanolone produces facilitation of GABAA receptor Cl− channel activity.

Mentions: GABAergic modulation of catecholamine release is also under a second level of control by adrenal cortical cells (Figure 6). The intra-adrenal portal vascular system (Coupland, 1975) drains the cortex that secretes steroid hormones including glucocorticoids and allopregnanolone. The portal system then enters the medulla, where chromaffin cells will be exposed to the secreted hormones at high concentrations (Wurtman, 2002). Hence, increased steroid release in response to stress or other stimuli will affect GABAergic modulation of catecholamine release; glucocorticoids by possibly enhancing the expression of GABAA α3 subunit and allopregnanolone by directly potentiating responses of GABAA receptor to low concentrations of GABA. Both of these actions would enhance the ability of low levels of GABA to induce release of catecholamines. However, they would also increase the ability of GABA to reduce release induced by high frequency nerve stimulation. These effects would integrate activation of the cortical cells (perhaps reflecting stress levels) with rapid effects of released catecholamines.


GABA Signaling and Neuroactive Steroids in Adrenal Medullary Chromaffin Cells.

Harada K, Matsuoka H, Fujihara H, Ueta Y, Yanagawa Y, Inoue M - Front Cell Neurosci (2016)

Summary of effects of adrenal cortical hormones on GABA signaling. The left image represents hematoxylin-eosin staining of mouse adrenal gland. GABA is stored in large dense core vesicles (LDCVs) or chromaffin granules in chromaffn cells. Glucocorticoids produce an increase in expression of α3-containing GABAA receptors whereas allopregnanolone produces facilitation of GABAA receptor Cl− channel activity.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4834308&req=5

Figure 6: Summary of effects of adrenal cortical hormones on GABA signaling. The left image represents hematoxylin-eosin staining of mouse adrenal gland. GABA is stored in large dense core vesicles (LDCVs) or chromaffin granules in chromaffn cells. Glucocorticoids produce an increase in expression of α3-containing GABAA receptors whereas allopregnanolone produces facilitation of GABAA receptor Cl− channel activity.
Mentions: GABAergic modulation of catecholamine release is also under a second level of control by adrenal cortical cells (Figure 6). The intra-adrenal portal vascular system (Coupland, 1975) drains the cortex that secretes steroid hormones including glucocorticoids and allopregnanolone. The portal system then enters the medulla, where chromaffin cells will be exposed to the secreted hormones at high concentrations (Wurtman, 2002). Hence, increased steroid release in response to stress or other stimuli will affect GABAergic modulation of catecholamine release; glucocorticoids by possibly enhancing the expression of GABAA α3 subunit and allopregnanolone by directly potentiating responses of GABAA receptor to low concentrations of GABA. Both of these actions would enhance the ability of low levels of GABA to induce release of catecholamines. However, they would also increase the ability of GABA to reduce release induced by high frequency nerve stimulation. These effects would integrate activation of the cortical cells (perhaps reflecting stress levels) with rapid effects of released catecholamines.

Bottom Line: 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.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 (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.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell and Systems Physiology, University of Occupational and Environmental Health School of Medicine Kitakyushu, Japan.

ABSTRACT
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 GABAA 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 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 (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.

No MeSH data available.


Related in: MedlinePlus