Negative modulation of the GABAAρ1 receptor function by histamine
Besides its function as a local mediator of the immune response, histamine can play a role as a neurotransmitter and neuromodulator. Histamine actions are classically mediated through four different G protein-coupled receptor subtypes but non-classical actions were also described, including effects...
| Autores principales: | , , , |
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| Formato: | Artículo |
| Lenguaje: | Inglés |
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Elsevier
2023
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| Acceso en línea: | http://hdl.handle.net/20.500.12123/14787 https://www.sciencedirect.com/science/article/pii/S0014299923003916 https://doi.org/10.1016/j.ejphar.2023.175880 |
| _version_ | 1855485429174763520 |
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| author | Beltrán González, Andrea N. López Pazos, Manuel I. Del Vas, Mariana Calvo, Daniel Juan |
| author_browse | Beltrán González, Andrea N. Calvo, Daniel Juan Del Vas, Mariana López Pazos, Manuel I. |
| author_facet | Beltrán González, Andrea N. López Pazos, Manuel I. Del Vas, Mariana Calvo, Daniel Juan |
| author_sort | Beltrán González, Andrea N. |
| collection | INTA Digital |
| description | Besides its function as a local mediator of the immune response, histamine can play a role as a neurotransmitter and neuromodulator. Histamine actions are classically mediated through four different G protein-coupled receptor subtypes but non-classical actions were also described, including effects on many ligand-gated ion channels. Previous evidence indicated that histamine acts as a positive modulator on diverse GABAA receptor subtypes, such as GABAAα1β2γ2, GABAAα2β3γ2, GABAAα3β3γ2, GABAAα4β3γ2 and GABAAα5β3γ2. Meanwhile, its effects on GABAAρ1 receptors, known to stand for tonic currents in retinal neurons, had not been examined before. The effects of histamine on the function of human homomeric GABAAρ1 receptors were studied here, using heterologous expression in Xenopus laevis oocytes followed by the electrophysiological recording of GABA-evoked Cl− currents. Histamine inhibited GABAAρ1 receptor-mediated responses. Effects were reversible, independent of the membrane potential, and strongly dependent on both histamine and GABA concentration. A rightward parallel shift in the concentration-response curve for GABA was observed in the presence of histamine, without substantial change in the maximal response or the Hill coefficient. Results were compatible with a competitive antagonism of histamine on the GABAAρ1 receptors. This is the first report of inhibitory actions exerted by histamine on an ionotropic GABA receptor. |
| format | Artículo |
| id | INTA14787 |
| institution | Instituto Nacional de Tecnología Agropecuaria (INTA -Argentina) |
| language | Inglés |
| publishDate | 2023 |
| publishDateRange | 2023 |
| publishDateSort | 2023 |
| publisher | Elsevier |
| publisherStr | Elsevier |
| record_format | dspace |
| spelling | INTA147872023-07-20T14:25:07Z Negative modulation of the GABAAρ1 receptor function by histamine Beltrán González, Andrea N. López Pazos, Manuel I. Del Vas, Mariana Calvo, Daniel Juan Histamina GABA Neurotransmisores Histamine Gamma-aminobutyric Acid Neurotransmitters Ácido Gamma-aminobutírico Besides its function as a local mediator of the immune response, histamine can play a role as a neurotransmitter and neuromodulator. Histamine actions are classically mediated through four different G protein-coupled receptor subtypes but non-classical actions were also described, including effects on many ligand-gated ion channels. Previous evidence indicated that histamine acts as a positive modulator on diverse GABAA receptor subtypes, such as GABAAα1β2γ2, GABAAα2β3γ2, GABAAα3β3γ2, GABAAα4β3γ2 and GABAAα5β3γ2. Meanwhile, its effects on GABAAρ1 receptors, known to stand for tonic currents in retinal neurons, had not been examined before. The effects of histamine on the function of human homomeric GABAAρ1 receptors were studied here, using heterologous expression in Xenopus laevis oocytes followed by the electrophysiological recording of GABA-evoked Cl− currents. Histamine inhibited GABAAρ1 receptor-mediated responses. Effects were reversible, independent of the membrane potential, and strongly dependent on both histamine and GABA concentration. A rightward parallel shift in the concentration-response curve for GABA was observed in the presence of histamine, without substantial change in the maximal response or the Hill coefficient. Results were compatible with a competitive antagonism of histamine on the GABAAρ1 receptors. This is the first report of inhibitory actions exerted by histamine on an ionotropic GABA receptor. Instituto de Biotecnología Fil: Beltrán González, Andrea N. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Fisiología, Biología Molecular y Neurociencias (IFIByNE). Laboratorio de Neurobiología Celular y Molecular; Argentina Fil: Beltrán González, Andrea N. Universidad de Buenos Aires. Instituto de Fisiología, Biología Molecular y Neurociencias (IFIByNE). Laboratorio de Neurobiología Celular y Molecular; Argentina Fil: López Pazos, Manuel I. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Fisiología, Biología Molecular y Neurociencias (IFIByNE). Laboratorio de Neurobiología Celular y Molecular; Argentina Fil: López Pazos, Manuel I. Universidad de Buenos Aires. Instituto de Fisiología, Biología Molecular y Neurociencias (IFIByNE). Laboratorio de Neurobiología Celular y Molecular; Argentina Fil: Del Vas, Mariana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina Fil: Del Vas, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Calvo, Daniel J. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Fisiología, Biología Molecular y Neurociencias (IFIByNE). Laboratorio de Neurobiología Celular y Molecular; Argentina Fil: Calvo, Daniel J. Universidad de Buenos Aires. Instituto de Fisiología, Biología Molecular y Neurociencias (IFIByNE). Laboratorio de Neurobiología Celular y Molecular; Argentina 2023-07-20T14:20:37Z 2023-07-20T14:20:37Z 2023-09 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/20.500.12123/14787 https://www.sciencedirect.com/science/article/pii/S0014299923003916 1879-0712 0014-2999 https://doi.org/10.1016/j.ejphar.2023.175880 eng info:eu-repo/semantics/restrictedAccess http://creativecommons.org/licenses/by-nc-sa/4.0/ Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) application/pdf Elsevier European Journal of Pharmacology 955 : 175880. (September 2023) |
| spellingShingle | Histamina GABA Neurotransmisores Histamine Gamma-aminobutyric Acid Neurotransmitters Ácido Gamma-aminobutírico Beltrán González, Andrea N. López Pazos, Manuel I. Del Vas, Mariana Calvo, Daniel Juan Negative modulation of the GABAAρ1 receptor function by histamine |
| title | Negative modulation of the GABAAρ1 receptor function by histamine |
| title_full | Negative modulation of the GABAAρ1 receptor function by histamine |
| title_fullStr | Negative modulation of the GABAAρ1 receptor function by histamine |
| title_full_unstemmed | Negative modulation of the GABAAρ1 receptor function by histamine |
| title_short | Negative modulation of the GABAAρ1 receptor function by histamine |
| title_sort | negative modulation of the gabaaρ1 receptor function by histamine |
| topic | Histamina GABA Neurotransmisores Histamine Gamma-aminobutyric Acid Neurotransmitters Ácido Gamma-aminobutírico |
| url | http://hdl.handle.net/20.500.12123/14787 https://www.sciencedirect.com/science/article/pii/S0014299923003916 https://doi.org/10.1016/j.ejphar.2023.175880 |
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