Different subtypes of GABA-A receptors are expressed in human, mouse and rat T lymphocytes.

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 b...

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Autores principales:	Suresh K Mendu, Amol Bhandage, Zhe Jin, Bryndis Birnir
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/74c902eb16854b2997e215b9f92c15ae
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spelling	oai:doaj.org-article:74c902eb16854b2997e215b9f92c15ae2021-11-18T07:08:07ZDifferent subtypes of GABA-A receptors are expressed in human, mouse and rat T lymphocytes.1932-620310.1371/journal.pone.0042959https://doaj.org/article/74c902eb16854b2997e215b9f92c15ae2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22927941/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203γ-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.Suresh K MenduAmol BhandageZhe JinBryndis BirnirPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 8, p e42959 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Suresh K Mendu Amol Bhandage Zhe Jin Bryndis Birnir Different subtypes of GABA-A receptors are expressed in human, mouse and rat T lymphocytes.
description	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.
format	article
author	Suresh K Mendu Amol Bhandage Zhe Jin Bryndis Birnir
author_facet	Suresh K Mendu Amol Bhandage Zhe Jin Bryndis Birnir
author_sort	Suresh K Mendu
title	Different subtypes of GABA-A receptors are expressed in human, mouse and rat T lymphocytes.
title_short	Different subtypes of GABA-A receptors are expressed in human, mouse and rat T lymphocytes.
title_full	Different subtypes of GABA-A receptors are expressed in human, mouse and rat T lymphocytes.
title_fullStr	Different subtypes of GABA-A receptors are expressed in human, mouse and rat T lymphocytes.
title_full_unstemmed	Different subtypes of GABA-A receptors are expressed in human, mouse and rat T lymphocytes.
title_sort	different subtypes of gaba-a receptors are expressed in human, mouse and rat t lymphocytes.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/74c902eb16854b2997e215b9f92c15ae
work_keys_str_mv	AT sureshkmendu differentsubtypesofgabaareceptorsareexpressedinhumanmouseandrattlymphocytes AT amolbhandage differentsubtypesofgabaareceptorsareexpressedinhumanmouseandrattlymphocytes AT zhejin differentsubtypesofgabaareceptorsareexpressedinhumanmouseandrattlymphocytes AT bryndisbirnir differentsubtypesofgabaareceptorsareexpressedinhumanmouseandrattlymphocytes
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Different subtypes of GABA-A receptors are expressed in human, mouse and rat T lymphocytes.

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