Endothelin-Mediated Calcium Responses in Supraoptic Nucleus Astrocytes Influence Magnocellular Neurosecretory Firing Activity

Autores
Filosa, J. A; Naskar, K.; Perfume, Guadalupe; Iddings, J. A.; Biancardi, V. C.; Vatta, Marcelo Sergio; Stern, Jorge Enrique
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In addition to their peripheral vasoactive effects, accumulating evidence supports an important role for endothelins (ETs) in the regulation of the hypothalamic magnocellular neurosecretory system, which produces and releases the neurohormones vasopressin (VP) and oxytocin (OT). Still, the precise cellular substrates, loci and mechanisms underlying the actions of ETs on the magnocellular system are poorly understood. In the present study, we combined patch-clamp electrophysiology, confocal Ca 2+ imaging and immunohistochemistry to study the actions of ETs on supraoptic nucleus (SON) magnocellular neurosecretory neurones and astrocytes. Our studies show that ET-1 evoked rises in [Ca 2+] i levels in SON astrocytes (but not neurones), an effect largely mediated by the activation of ET B receptors and mobilisation of thapsigargin-sensitive Ca 2+ stores. The presence of ET B receptors in SON astrocytes was also verified immunohistochemically. ET B receptor activation either increased (75%) or decreased (25%) SON firing activity, both in VP and putative OT neurones, and these effects were prevented when slices were preincubated in glutamate receptor blockers or nitric oxide synthase blockers, respectively. Moreover, ET B-mediated effects in SON neurones were also prevented by a gliotoxin compound, and when changes in [Ca 2+] i were prevented with bath-applied BAPTA-AM or thapsigargin. Conversely, intracellular Ca 2+ chelation in the recorded SON neurones failed to block ET B-mediated effects. In summary, our results indicate that ET B receptor activation in SON astrocytes induces the mobilisation of [Ca 2+] i, likely resulting in the activation of glutamate and nitric oxide signalling pathways, evoking in turn excitatory and inhibitory SON neuronal responses, respectively. Taken together, our study supports an important role for astrocytes in mediating the actions of ETs on the magnocellular neurosecretory system. © 2011 The Authors. Journal of Neuroendocrinology © 2011 Blackwell Publishing Ltd.
Fil: Filosa, J. A. Georgia Health Sciences University; Estados Unidos
Fil: Naskar, K.. Georgia Health Sciences University; Estados Unidos
Fil: Perfume, Guadalupe. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina
Fil: Iddings, J. A.. Georgia Health Sciences University; Estados Unidos
Fil: Biancardi, V. C.. Georgia Health Sciences University; Estados Unidos
Fil: Vatta, Marcelo Sergio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina
Fil: Stern, Jorge Enrique. Georgia Health Sciences University; Estados Unidos
Materia
Endothelins
Glia
Hypothalamus
Oxytocin
Vasopressin
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/67398

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network_name_str CONICET Digital (CONICET)
spelling Endothelin-Mediated Calcium Responses in Supraoptic Nucleus Astrocytes Influence Magnocellular Neurosecretory Firing ActivityFilosa, J. ANaskar, K.Perfume, GuadalupeIddings, J. A.Biancardi, V. C.Vatta, Marcelo SergioStern, Jorge EnriqueEndothelinsGliaHypothalamusOxytocinVasopressinhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3In addition to their peripheral vasoactive effects, accumulating evidence supports an important role for endothelins (ETs) in the regulation of the hypothalamic magnocellular neurosecretory system, which produces and releases the neurohormones vasopressin (VP) and oxytocin (OT). Still, the precise cellular substrates, loci and mechanisms underlying the actions of ETs on the magnocellular system are poorly understood. In the present study, we combined patch-clamp electrophysiology, confocal Ca 2+ imaging and immunohistochemistry to study the actions of ETs on supraoptic nucleus (SON) magnocellular neurosecretory neurones and astrocytes. Our studies show that ET-1 evoked rises in [Ca 2+] i levels in SON astrocytes (but not neurones), an effect largely mediated by the activation of ET B receptors and mobilisation of thapsigargin-sensitive Ca 2+ stores. The presence of ET B receptors in SON astrocytes was also verified immunohistochemically. ET B receptor activation either increased (75%) or decreased (25%) SON firing activity, both in VP and putative OT neurones, and these effects were prevented when slices were preincubated in glutamate receptor blockers or nitric oxide synthase blockers, respectively. Moreover, ET B-mediated effects in SON neurones were also prevented by a gliotoxin compound, and when changes in [Ca 2+] i were prevented with bath-applied BAPTA-AM or thapsigargin. Conversely, intracellular Ca 2+ chelation in the recorded SON neurones failed to block ET B-mediated effects. In summary, our results indicate that ET B receptor activation in SON astrocytes induces the mobilisation of [Ca 2+] i, likely resulting in the activation of glutamate and nitric oxide signalling pathways, evoking in turn excitatory and inhibitory SON neuronal responses, respectively. Taken together, our study supports an important role for astrocytes in mediating the actions of ETs on the magnocellular neurosecretory system. © 2011 The Authors. Journal of Neuroendocrinology © 2011 Blackwell Publishing Ltd.Fil: Filosa, J. A. Georgia Health Sciences University; Estados UnidosFil: Naskar, K.. Georgia Health Sciences University; Estados UnidosFil: Perfume, Guadalupe. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: Iddings, J. A.. Georgia Health Sciences University; Estados UnidosFil: Biancardi, V. C.. Georgia Health Sciences University; Estados UnidosFil: Vatta, Marcelo Sergio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: Stern, Jorge Enrique. Georgia Health Sciences University; Estados UnidosWiley Blackwell Publishing, Inc2012-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/67398Filosa, J. A; Naskar, K.; Perfume, Guadalupe; Iddings, J. A.; Biancardi, V. C.; et al.; Endothelin-Mediated Calcium Responses in Supraoptic Nucleus Astrocytes Influence Magnocellular Neurosecretory Firing Activity; Wiley Blackwell Publishing, Inc; Journal of Neuroendocrinology; 24; 2; 2-2012; 378-3920953-8194CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2826.2011.02243.xinfo:eu-repo/semantics/altIdentifier/doi/10.1111/j.1365-2826.2011.02243.xinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:55:21Zoai:ri.conicet.gov.ar:11336/67398instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:55:21.476CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Endothelin-Mediated Calcium Responses in Supraoptic Nucleus Astrocytes Influence Magnocellular Neurosecretory Firing Activity
title Endothelin-Mediated Calcium Responses in Supraoptic Nucleus Astrocytes Influence Magnocellular Neurosecretory Firing Activity
spellingShingle Endothelin-Mediated Calcium Responses in Supraoptic Nucleus Astrocytes Influence Magnocellular Neurosecretory Firing Activity
Filosa, J. A
Endothelins
Glia
Hypothalamus
Oxytocin
Vasopressin
title_short Endothelin-Mediated Calcium Responses in Supraoptic Nucleus Astrocytes Influence Magnocellular Neurosecretory Firing Activity
title_full Endothelin-Mediated Calcium Responses in Supraoptic Nucleus Astrocytes Influence Magnocellular Neurosecretory Firing Activity
title_fullStr Endothelin-Mediated Calcium Responses in Supraoptic Nucleus Astrocytes Influence Magnocellular Neurosecretory Firing Activity
title_full_unstemmed Endothelin-Mediated Calcium Responses in Supraoptic Nucleus Astrocytes Influence Magnocellular Neurosecretory Firing Activity
title_sort Endothelin-Mediated Calcium Responses in Supraoptic Nucleus Astrocytes Influence Magnocellular Neurosecretory Firing Activity
dc.creator.none.fl_str_mv Filosa, J. A
Naskar, K.
Perfume, Guadalupe
Iddings, J. A.
Biancardi, V. C.
Vatta, Marcelo Sergio
Stern, Jorge Enrique
author Filosa, J. A
author_facet Filosa, J. A
Naskar, K.
Perfume, Guadalupe
Iddings, J. A.
Biancardi, V. C.
Vatta, Marcelo Sergio
Stern, Jorge Enrique
author_role author
author2 Naskar, K.
Perfume, Guadalupe
Iddings, J. A.
Biancardi, V. C.
Vatta, Marcelo Sergio
Stern, Jorge Enrique
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Endothelins
Glia
Hypothalamus
Oxytocin
Vasopressin
topic Endothelins
Glia
Hypothalamus
Oxytocin
Vasopressin
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv In addition to their peripheral vasoactive effects, accumulating evidence supports an important role for endothelins (ETs) in the regulation of the hypothalamic magnocellular neurosecretory system, which produces and releases the neurohormones vasopressin (VP) and oxytocin (OT). Still, the precise cellular substrates, loci and mechanisms underlying the actions of ETs on the magnocellular system are poorly understood. In the present study, we combined patch-clamp electrophysiology, confocal Ca 2+ imaging and immunohistochemistry to study the actions of ETs on supraoptic nucleus (SON) magnocellular neurosecretory neurones and astrocytes. Our studies show that ET-1 evoked rises in [Ca 2+] i levels in SON astrocytes (but not neurones), an effect largely mediated by the activation of ET B receptors and mobilisation of thapsigargin-sensitive Ca 2+ stores. The presence of ET B receptors in SON astrocytes was also verified immunohistochemically. ET B receptor activation either increased (75%) or decreased (25%) SON firing activity, both in VP and putative OT neurones, and these effects were prevented when slices were preincubated in glutamate receptor blockers or nitric oxide synthase blockers, respectively. Moreover, ET B-mediated effects in SON neurones were also prevented by a gliotoxin compound, and when changes in [Ca 2+] i were prevented with bath-applied BAPTA-AM or thapsigargin. Conversely, intracellular Ca 2+ chelation in the recorded SON neurones failed to block ET B-mediated effects. In summary, our results indicate that ET B receptor activation in SON astrocytes induces the mobilisation of [Ca 2+] i, likely resulting in the activation of glutamate and nitric oxide signalling pathways, evoking in turn excitatory and inhibitory SON neuronal responses, respectively. Taken together, our study supports an important role for astrocytes in mediating the actions of ETs on the magnocellular neurosecretory system. © 2011 The Authors. Journal of Neuroendocrinology © 2011 Blackwell Publishing Ltd.
Fil: Filosa, J. A. Georgia Health Sciences University; Estados Unidos
Fil: Naskar, K.. Georgia Health Sciences University; Estados Unidos
Fil: Perfume, Guadalupe. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina
Fil: Iddings, J. A.. Georgia Health Sciences University; Estados Unidos
Fil: Biancardi, V. C.. Georgia Health Sciences University; Estados Unidos
Fil: Vatta, Marcelo Sergio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina
Fil: Stern, Jorge Enrique. Georgia Health Sciences University; Estados Unidos
description In addition to their peripheral vasoactive effects, accumulating evidence supports an important role for endothelins (ETs) in the regulation of the hypothalamic magnocellular neurosecretory system, which produces and releases the neurohormones vasopressin (VP) and oxytocin (OT). Still, the precise cellular substrates, loci and mechanisms underlying the actions of ETs on the magnocellular system are poorly understood. In the present study, we combined patch-clamp electrophysiology, confocal Ca 2+ imaging and immunohistochemistry to study the actions of ETs on supraoptic nucleus (SON) magnocellular neurosecretory neurones and astrocytes. Our studies show that ET-1 evoked rises in [Ca 2+] i levels in SON astrocytes (but not neurones), an effect largely mediated by the activation of ET B receptors and mobilisation of thapsigargin-sensitive Ca 2+ stores. The presence of ET B receptors in SON astrocytes was also verified immunohistochemically. ET B receptor activation either increased (75%) or decreased (25%) SON firing activity, both in VP and putative OT neurones, and these effects were prevented when slices were preincubated in glutamate receptor blockers or nitric oxide synthase blockers, respectively. Moreover, ET B-mediated effects in SON neurones were also prevented by a gliotoxin compound, and when changes in [Ca 2+] i were prevented with bath-applied BAPTA-AM or thapsigargin. Conversely, intracellular Ca 2+ chelation in the recorded SON neurones failed to block ET B-mediated effects. In summary, our results indicate that ET B receptor activation in SON astrocytes induces the mobilisation of [Ca 2+] i, likely resulting in the activation of glutamate and nitric oxide signalling pathways, evoking in turn excitatory and inhibitory SON neuronal responses, respectively. Taken together, our study supports an important role for astrocytes in mediating the actions of ETs on the magnocellular neurosecretory system. © 2011 The Authors. Journal of Neuroendocrinology © 2011 Blackwell Publishing Ltd.
publishDate 2012
dc.date.none.fl_str_mv 2012-02
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
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info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/67398
Filosa, J. A; Naskar, K.; Perfume, Guadalupe; Iddings, J. A.; Biancardi, V. C.; et al.; Endothelin-Mediated Calcium Responses in Supraoptic Nucleus Astrocytes Influence Magnocellular Neurosecretory Firing Activity; Wiley Blackwell Publishing, Inc; Journal of Neuroendocrinology; 24; 2; 2-2012; 378-392
0953-8194
CONICET Digital
CONICET
url http://hdl.handle.net/11336/67398
identifier_str_mv Filosa, J. A; Naskar, K.; Perfume, Guadalupe; Iddings, J. A.; Biancardi, V. C.; et al.; Endothelin-Mediated Calcium Responses in Supraoptic Nucleus Astrocytes Influence Magnocellular Neurosecretory Firing Activity; Wiley Blackwell Publishing, Inc; Journal of Neuroendocrinology; 24; 2; 2-2012; 378-392
0953-8194
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
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repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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