ATP antagonizes thrombin-induced signal transduction through 12(S)-HETE and cAMP.

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 extracell...

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Autores principales:	Jaione Burzaco, Manuel Conde, Luis A Parada, José L Zugaza, Jean-Paul Dehaye, Aida Marino
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b3727217a0ad485dac282289d9faba5e
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spelling	oai:doaj.org-article:b3727217a0ad485dac282289d9faba5e2021-11-18T07:40:20ZATP antagonizes thrombin-induced signal transduction through 12(S)-HETE and cAMP.1932-620310.1371/journal.pone.0067117https://doaj.org/article/b3727217a0ad485dac282289d9faba5e2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23826207/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203In 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 [Ca(2+)]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.Jaione BurzacoManuel CondeLuis A ParadaJosé L ZugazaJean-Paul DehayeAida MarinoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 6, p e67117 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jaione Burzaco Manuel Conde Luis A Parada José L Zugaza Jean-Paul Dehaye Aida Marino ATP antagonizes thrombin-induced signal transduction through 12(S)-HETE and cAMP.
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 [Ca(2+)]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.
format	article
author	Jaione Burzaco Manuel Conde Luis A Parada José L Zugaza Jean-Paul Dehaye Aida Marino
author_facet	Jaione Burzaco Manuel Conde Luis A Parada José L Zugaza Jean-Paul Dehaye Aida Marino
author_sort	Jaione Burzaco
title	ATP antagonizes thrombin-induced signal transduction through 12(S)-HETE and cAMP.
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.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/b3727217a0ad485dac282289d9faba5e
work_keys_str_mv	AT jaioneburzaco atpantagonizesthrombininducedsignaltransductionthrough12sheteandcamp AT manuelconde atpantagonizesthrombininducedsignaltransductionthrough12sheteandcamp AT luisaparada atpantagonizesthrombininducedsignaltransductionthrough12sheteandcamp AT joselzugaza atpantagonizesthrombininducedsignaltransductionthrough12sheteandcamp AT jeanpauldehaye atpantagonizesthrombininducedsignaltransductionthrough12sheteandcamp AT aidamarino atpantagonizesthrombininducedsignaltransductionthrough12sheteandcamp
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ATP antagonizes thrombin-induced signal transduction through 12(S)-HETE and cAMP.

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