GABA in peripheral tissues: Presence and actions in endocrine pancreatic function

Gerber, J; Hare, Theodore A.

doi:10.1016/0361-9230(80)90055-6

Cited by 32 publications

(6 citation statements)

References 16 publications

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“…Despite numerous experiments, the physiological role of GABA in the B cell is still unclear, and it is still not known if this amino acid functions as an endocrine/ paracrine, or intracellular modulatory substance. The release of GABA in media containing high glucose concentrations has already been reported in the rat pancreas [9]. GABA-immunoreactivity in the secretory granules would mean that GABA is co-secreted with insulin, and would support the endocrine/paracrine role.…”

Section: Discussionmentioning

confidence: 59%

Immunocytochemical localisation of GABA in endocrine cells of the rat entero-pancreatic system

Gilon

1988

Biology of the Cell

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The occurrence of GABA-containing cells in the rat entero-pancreatic system was investigated by using anti-GABA-glutaraldehyde antibodies at the light and electron microscope level. In the pancreas, the B cells showed intense immunoreactivity, contrary to non-B and exocrine cells. Moreover, post-embedding immunogold staining was localised mostly in mitochondria, close to rough endoplasmic reticulum and in the nucleus. The insulin granules appeared nonsignificantly stained, which suggests the lack of cosecretion of GABA together with insulin. In the duodenum, GABA immunoreactivity was detected in certain endocrine cell types, suggesting a possible interaction with this amino acid. The well established GABAergic innervation in the enteric system was also confirmed by immunolabelling.

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Section: Discussionmentioning

confidence: 59%

Immunocytochemical localisation of GABA in endocrine cells of the rat entero-pancreatic system

Gilon

1988

Biology of the Cell

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“…The proposed source of GABA is ␤ cells, which may coordinately release it with insulin (20). Since glutamate/aspartate uptake activity was predominantly in ␣ cells, we tested whether glucose inhibition of glutamate transport might be mediated through this mechanism.…”

Section: Resultsmentioning

confidence: 99%

A High Affinity Glutamate/Aspartate Transport System in Pancreatic Islets of Langerhans Modulates Glucose-stimulated Insulin Secretion

Weaver

Gundersen

Verdoorn

1998

Journal of Biological Chemistry

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To examine the role of glutamatergic signaling in the function of pancreatic islets, we have characterized a high affinity glutamate/aspartate uptake system in this tissue. The islet [3 H]glutamate uptake activity was Na ؉ -dependent, and it was blocked by L-trans-pyrrolidine-2,4-dicarboxylic acid, a blocker of neuronal and glial glutamate transporters. Islet glutamate transport activity exhibited a V max of 8.48 ؎ 1.47 fmol/min/islet (n ‫؍‬ 4), which corresponds to 102.2 ؎ 17.7 pmol/min/mg islet protein. The apparent K m of islet glutamate transport activity depended on the glucose concentration used in the assay. In the presence of glucose concentrations that do not stimulate insulin secretion (2.8 mM), the apparent K m was 34.7 ؎ 7.8 M (n ‫؍‬ 3). However, in high glucose (16.7 mM) the apparent K m increased to 112.7 ؎ 16.5 M (n ‫؍‬ 3) with little or no change in V max . Like most known plasma membrane glutamate transporters, islet glutamate transporters also transported D-aspartate. Anti-Daspartate immunoreactivity showed that the islet glutamate/aspartate transport activity was localized to the non-␤ cell islet mantle. In perifusion experiments with isolated islets in the absence of exogenous amino acids, L-trans-pyrrolidine-2,4-dicarboxylic acid in the presence of 8.3 mM glucose potentiated insulin secretion 23.3 ؎ 2.3% (n ‫؍‬ 3) compared with 8.3 mM glucose alone. This effect was abolished in the presence of the ␣-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione. Furthermore, 6-cyano-7-nitroquinoxaline-2,3-dione alone inhibited glucose-stimulated insulin secretion in isolated islets by 15.9 ؎ 5.9% (n ‫؍‬ 3). Taken together these data suggest that a high affinity glutamate transport system exists in pancreatic islets and that this system contributes to a glutamatergic signaling pathway that can modulate glucose-inducible insulin secretion.Although the role of glutamate as a signaling molecule is well established in the central nervous system, a similar role in the periphery has only recently been suggested. We (1) and others (2) have detected functional glutamate receptors in the pancreatic islets of Langerhans. These miniature organs, found dispersed throughout the exocrine pancreas, are composed of four major cell types as follows: the insulin-secreting ␤ cell, the glucagon-secreting ␣ cell, the pancreatic polypeptide-secreting PP cell, and the somatostatin-secreting ␦ cell. The electrically excitable ␤ cells are stimulated to secrete insulin in response to changes in serum glucose concentrations. Secretion of insulin, and the three other major peptide hormones found in islets, is also believed to be affected by other metabolic and neuronal signals (reviewed in Refs. 3 and 4). Bertrand et al. (5,6) have shown that ␣-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) 1 receptor agonists can potentiate both insulin and glucagon secretion from a perfused pancreas preparation and that oral or intravenous glutamate can increase insulin secretio...

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“…GABA is present in blood in submicromolar concentration [15] , [16] and may be produced by the immune cells themselves [7] , [17] . Immune cells such as CD4 + , CD8 + T cells and macrophages do express GABA-A channels [6] , [7] , [9] , [11] , [18] , [19] but what subtypes are present is generally not known.…”

Section: Introductionmentioning

confidence: 99%

Different Subtypes of GABA-A Receptors Are Expressed in Human, Mouse and Rat T Lymphocytes

Mendu¹,

Bhandage²,

Jin³

et al. 2012

PLoS ONE

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γ-aminobutyric acid (GABA) is the most prominent neuroinhibitory transmitter in the brain, where it activates neuronal GABA-A receptors (GABA-A channels) located at synapses and outside of synapses. The GABA-A receptors are primary targets of many clinically useful drugs. In recent years, GABA has been shown to act as an immunomodulatory molecule. We have examined in human, mouse and rat CD4+ and CD8+ T cells which subunit isoforms of the GABA-A channels are expressed. The channel physiology and drug specificity is dictated by the GABA-A receptor subtype, which in turn is determined by the subunit isoforms that make the channel. There were 5, 8 and 13 different GABA-A subunit isoforms identified in human, mouse and rat CD4+ and CD8+ T cells, respectively. Importantly, the γ2 subunit that imposes benzodiazepine sensitivity on the GABA-A receptors, was only detected in the mouse T cells. Immunoblots and immunocytochemistry showed abundant GABA-A channel proteins in the T cells from all three species. GABA-activated whole-cell transient and tonic currents were recorded. The currents were inhibited by picrotoxin, SR95531 and bicuculline, antagonists of GABA-A channels. Clearly, in both humans and rodents T cells, functional GABA-A channels are expressed but the subtypes vary. It is important to bear in mind the interspecies difference when selecting the appropriate animal models to study the physiological role and pharmacological properties of GABA-A channels in CD4+ and CD8+ T cells and when selecting drugs aimed at modulating the human T cells function.

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GABA in peripheral tissues: Presence and actions in endocrine pancreatic function

Cited by 32 publications

References 16 publications

Immunocytochemical localisation of GABA in endocrine cells of the rat entero-pancreatic system

Immunocytochemical localisation of GABA in endocrine cells of the rat entero-pancreatic system

A High Affinity Glutamate/Aspartate Transport System in Pancreatic Islets of Langerhans Modulates Glucose-stimulated Insulin Secretion

Different Subtypes of GABA-A Receptors Are Expressed in Human, Mouse and Rat T Lymphocytes

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