ATP Antagonizes Thrombin-Induced Signal Transduction through 12(S)-HETE and cAMP

Autores
Burzaco, Jaione; Conde, Manuel; Parada, Luis Antonio; Zugaza, José L.; Dehaye, Jean-Paul; Marino, Aída
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In this study we have investigated the role of extracellular ATP on thrombin induced-platelet aggregation (TIPA) in washed human platelets. ATP inhibited TIPA in a dose-dependent manner and this inhibition was abolished by apyrase but not by adenosine deaminase (ADA) and it was reversed by extracellular magnesium. Antagonists of P2Y1 and P2Y12 receptors had no effect on this inhibition suggesting that a P2X receptor controlled ATP-mediated TIPA inhibition. ATP also blocked inositol phosphates (IP1, IP2, IP3) generation and [Ca2+]i mobilization induced by thrombin. Thrombin reduced cAMP levels which were restored in the presence of ATP. SQ-22536, an adenylate cyclase (AC) inhibitor, partially reduced the inhibition exerted by ATP on TIPA. 12-lipoxygenase (12-LO) inhibitors, nordihidroguaretic acid (NDGA) and 15(S)-hydroxy-5,8,11,13- eicosatetraenoic acid (15(S)-HETE), strongly prevented ATP-mediated TIPA inhibition. Additionally, ATP inhibited the increase of 12(S)-hydroxy-5,8,10,14-eicosatetraenoic acid (12(S)-HETE) induced by thrombin. Pretreatment with both SQ- 22536 and NDGA almost completely abolished ATP-mediated TIPA inhibition. Our results describe for the first time that ATP implicates both AC and 12-LO pathways in the inhibition of human platelets aggregation in response to agonists.
Fil: Burzaco, Jaione. UNIVERSIDAD DEL PAIS VASCO;
Fil: Conde, Manuel. UNIVERSIDAD DEL PAIS VASCO;
Fil: Parada, Luis Antonio. Consejo Nacional de Invest.cientif.y Tecnicas. Centro Cientifico Tecnol.conicet - Salta. Instituto de Patologia Experimental;
Fil: Zugaza, José L.. UNIVERSIDAD DEL PAIS VASCO;
Fil: Dehaye, Jean-Paul. UNIVERSIDAD DEL PAIS VASCO;
Fil: Marino, Aída. UNIVERSIDAD DEL PAIS VASCO;
Materia
Trombin
Platelet aggregation
ATP
Signalling
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:11336/545
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/545
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling ATP Antagonizes Thrombin-Induced Signal Transduction through 12(S)-HETE and cAMPBurzaco, JaioneConde, ManuelParada, Luis AntonioZugaza, José L.Dehaye, Jean-PaulMarino, AídaTrombinPlatelet aggregationATPSignallinghttps://purl.org/becyt/ford/1https://purl.org/becyt/ford/1.6In this study we have investigated the role of extracellular ATP on thrombin induced-platelet aggregation (TIPA) in washed human platelets. ATP inhibited TIPA in a dose-dependent manner and this inhibition was abolished by apyrase but not by adenosine deaminase (ADA) and it was reversed by extracellular magnesium. Antagonists of P2Y1 and P2Y12 receptors had no effect on this inhibition suggesting that a P2X receptor controlled ATP-mediated TIPA inhibition. ATP also blocked inositol phosphates (IP1, IP2, IP3) generation and [Ca2+]i mobilization induced by thrombin. Thrombin reduced cAMP levels which were restored in the presence of ATP. SQ-22536, an adenylate cyclase (AC) inhibitor, partially reduced the inhibition exerted by ATP on TIPA. 12-lipoxygenase (12-LO) inhibitors, nordihidroguaretic acid (NDGA) and 15(S)-hydroxy-5,8,11,13- eicosatetraenoic acid (15(S)-HETE), strongly prevented ATP-mediated TIPA inhibition. Additionally, ATP inhibited the increase of 12(S)-hydroxy-5,8,10,14-eicosatetraenoic acid (12(S)-HETE) induced by thrombin. Pretreatment with both SQ- 22536 and NDGA almost completely abolished ATP-mediated TIPA inhibition. Our results describe for the first time that ATP implicates both AC and 12-LO pathways in the inhibition of human platelets aggregation in response to agonists.Fil: Burzaco, Jaione. UNIVERSIDAD DEL PAIS VASCO;Fil: Conde, Manuel. UNIVERSIDAD DEL PAIS VASCO;Fil: Parada, Luis Antonio. Consejo Nacional de Invest.cientif.y Tecnicas. Centro Cientifico Tecnol.conicet - Salta. Instituto de Patologia Experimental;Fil: Zugaza, José L.. UNIVERSIDAD DEL PAIS VASCO;Fil: Dehaye, Jean-Paul. UNIVERSIDAD DEL PAIS VASCO;Fil: Marino, Aída. UNIVERSIDAD DEL PAIS VASCO;Public Library Science2013-06-24info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/545Burzaco, Jaione; Conde, Manuel; Parada, Luis Antonio; Zugaza, José L.; Dehaye, Jean-Paul; Marino, Aída; ATP Antagonizes Thrombin-Induced Signal Transduction through 12(S)-HETE and cAMP; Public Library Science; Plos One; 8; 24-6-2013; 67117-67118;1932-6203enginfo:eu-repo/semantics/altIdentifier/url/http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0067117info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:46:47Zoai:ri.conicet.gov.ar:11336/545instacron: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:34982025-09-29 10:46:48.04CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv ATP Antagonizes Thrombin-Induced Signal Transduction through 12(S)-HETE and cAMP
title ATP Antagonizes Thrombin-Induced Signal Transduction through 12(S)-HETE and cAMP
spellingShingle ATP Antagonizes Thrombin-Induced Signal Transduction through 12(S)-HETE and cAMP
Burzaco, Jaione
Trombin
Platelet aggregation
ATP
Signalling
title_short ATP Antagonizes Thrombin-Induced Signal Transduction through 12(S)-HETE and cAMP
title_full ATP Antagonizes Thrombin-Induced Signal Transduction through 12(S)-HETE and cAMP
title_fullStr ATP Antagonizes Thrombin-Induced Signal Transduction through 12(S)-HETE and cAMP
title_full_unstemmed ATP Antagonizes Thrombin-Induced Signal Transduction through 12(S)-HETE and cAMP
title_sort ATP Antagonizes Thrombin-Induced Signal Transduction through 12(S)-HETE and cAMP
dc.creator.none.fl_str_mv Burzaco, Jaione
Conde, Manuel
Parada, Luis Antonio
Zugaza, José L.
Dehaye, Jean-Paul
Marino, Aída
author Burzaco, Jaione
author_facet Burzaco, Jaione
Conde, Manuel
Parada, Luis Antonio
Zugaza, José L.
Dehaye, Jean-Paul
Marino, Aída
author_role author
author2 Conde, Manuel
Parada, Luis Antonio
Zugaza, José L.
Dehaye, Jean-Paul
Marino, Aída
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Trombin
Platelet aggregation
ATP
Signalling
topic Trombin
Platelet aggregation
ATP
Signalling
purl_subject.fl_str_mv https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/1.6
dc.description.none.fl_txt_mv In this study we have investigated the role of extracellular ATP on thrombin induced-platelet aggregation (TIPA) in washed human platelets. ATP inhibited TIPA in a dose-dependent manner and this inhibition was abolished by apyrase but not by adenosine deaminase (ADA) and it was reversed by extracellular magnesium. Antagonists of P2Y1 and P2Y12 receptors had no effect on this inhibition suggesting that a P2X receptor controlled ATP-mediated TIPA inhibition. ATP also blocked inositol phosphates (IP1, IP2, IP3) generation and [Ca2+]i mobilization induced by thrombin. Thrombin reduced cAMP levels which were restored in the presence of ATP. SQ-22536, an adenylate cyclase (AC) inhibitor, partially reduced the inhibition exerted by ATP on TIPA. 12-lipoxygenase (12-LO) inhibitors, nordihidroguaretic acid (NDGA) and 15(S)-hydroxy-5,8,11,13- eicosatetraenoic acid (15(S)-HETE), strongly prevented ATP-mediated TIPA inhibition. Additionally, ATP inhibited the increase of 12(S)-hydroxy-5,8,10,14-eicosatetraenoic acid (12(S)-HETE) induced by thrombin. Pretreatment with both SQ- 22536 and NDGA almost completely abolished ATP-mediated TIPA inhibition. Our results describe for the first time that ATP implicates both AC and 12-LO pathways in the inhibition of human platelets aggregation in response to agonists.
Fil: Burzaco, Jaione. UNIVERSIDAD DEL PAIS VASCO;
Fil: Conde, Manuel. UNIVERSIDAD DEL PAIS VASCO;
Fil: Parada, Luis Antonio. Consejo Nacional de Invest.cientif.y Tecnicas. Centro Cientifico Tecnol.conicet - Salta. Instituto de Patologia Experimental;
Fil: Zugaza, José L.. UNIVERSIDAD DEL PAIS VASCO;
Fil: Dehaye, Jean-Paul. UNIVERSIDAD DEL PAIS VASCO;
Fil: Marino, Aída. UNIVERSIDAD DEL PAIS VASCO;
description In this study we have investigated the role of extracellular ATP on thrombin induced-platelet aggregation (TIPA) in washed human platelets. ATP inhibited TIPA in a dose-dependent manner and this inhibition was abolished by apyrase but not by adenosine deaminase (ADA) and it was reversed by extracellular magnesium. Antagonists of P2Y1 and P2Y12 receptors had no effect on this inhibition suggesting that a P2X receptor controlled ATP-mediated TIPA inhibition. ATP also blocked inositol phosphates (IP1, IP2, IP3) generation and [Ca2+]i mobilization induced by thrombin. Thrombin reduced cAMP levels which were restored in the presence of ATP. SQ-22536, an adenylate cyclase (AC) inhibitor, partially reduced the inhibition exerted by ATP on TIPA. 12-lipoxygenase (12-LO) inhibitors, nordihidroguaretic acid (NDGA) and 15(S)-hydroxy-5,8,11,13- eicosatetraenoic acid (15(S)-HETE), strongly prevented ATP-mediated TIPA inhibition. Additionally, ATP inhibited the increase of 12(S)-hydroxy-5,8,10,14-eicosatetraenoic acid (12(S)-HETE) induced by thrombin. Pretreatment with both SQ- 22536 and NDGA almost completely abolished ATP-mediated TIPA inhibition. Our results describe for the first time that ATP implicates both AC and 12-LO pathways in the inhibition of human platelets aggregation in response to agonists.
publishDate 2013
dc.date.none.fl_str_mv 2013-06-24
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/545
Burzaco, Jaione; Conde, Manuel; Parada, Luis Antonio; Zugaza, José L.; Dehaye, Jean-Paul; Marino, Aída; ATP Antagonizes Thrombin-Induced Signal Transduction through 12(S)-HETE and cAMP; Public Library Science; Plos One; 8; 24-6-2013; 67117-67118;
1932-6203
url http://hdl.handle.net/11336/545
identifier_str_mv Burzaco, Jaione; Conde, Manuel; Parada, Luis Antonio; Zugaza, José L.; Dehaye, Jean-Paul; Marino, Aída; ATP Antagonizes Thrombin-Induced Signal Transduction through 12(S)-HETE and cAMP; Public Library Science; Plos One; 8; 24-6-2013; 67117-67118;
1932-6203
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0067117
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Public Library Science
publisher.none.fl_str_mv Public Library Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
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
_version_ 1844614510496710656
score 13.070432

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