Inhibition of one-chain and two-chain forms of human tissue-type plasminogen activator by the fast-acting inhibitor of plasminogen activator in vitro and in vivo

The inhibition of one-chain and two-chain molecular forms of human tissue-type plasminogen activator (t-PA) by the fast-acting inhibitor of plasminogen activator (PA-inhibitor) present in plasma was studied in vitro and in vivo in rabbits. In vitro, both one-chain and two-chain forms of t-PA were ne...

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Autores: Colucci, M. (M.)|||/items/4eda9c08-b77a-450e-b65a-1e4858fda75a, Páramo-Fernández, J.A. (José Antonio)|||/items/8c56baa6-2a43-4836-b91b-4eed15be3c96, Collen, D. (D.)|||/items/879361bf-d2c1-4d21-b62e-dd439ac8e527
Tipo de recurso: artículo
Fecha de publicación:1986
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/22923
Acceso en línea:https://hdl.handle.net/10171/22923
Access Level:acceso abierto
Palabra clave:Plasminogen Activators/antagonists & inhibitors
Plasminogen Inactivators
Tissue Plasminogen Activator/antagonists & inhibitors
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spelling Inhibition of one-chain and two-chain forms of human tissue-type plasminogen activator by the fast-acting inhibitor of plasminogen activator in vitro and in vivoColucci, M. (M.)|||/items/4eda9c08-b77a-450e-b65a-1e4858fda75aPáramo-Fernández, J.A. (José Antonio)|||/items/8c56baa6-2a43-4836-b91b-4eed15be3c96Collen, D. (D.)|||/items/879361bf-d2c1-4d21-b62e-dd439ac8e527Plasminogen Activators/antagonists & inhibitorsPlasminogen InactivatorsTissue Plasminogen Activator/antagonists & inhibitorsThe inhibition of one-chain and two-chain molecular forms of human tissue-type plasminogen activator (t-PA) by the fast-acting inhibitor of plasminogen activator (PA-inhibitor) present in plasma was studied in vitro and in vivo in rabbits. In vitro, both one-chain and two-chain forms of t-PA were neutralized very rapidly in rabbit plasma with high levels of PA-inhibitor. The rate constant of the interaction between two-chain t-PA and PA-inhibitor was estimated to be 3.10(7) L/mol/sec. The presence of CNBr-digested fibrinogen, which mimics the effect of fibrin on the activation of plasminogen by t-PA, did not influence the rate constant. Moreover, PA-inhibitor-rich plasma inhibited in a very similar way in vitro thrombolysis by one-chain or two-chain t-PA incorporated into the clot. Injection of one-chain or two-chain t-PA into rabbits with increased levels of PA-inhibitor, induced by endotoxin, resulted in very rapid inhibition of t-PA activity. Within 30 seconds after injection, no residual free t-PA could be demonstrated. Gel filtration analysis showed that the disappearance of t-PA activity was associated with the generation of t-PA-PA-inhibitor complex with an apparent Mr of 100,000. This enzyme-inhibitor complex, like free t-PA, was cleared from the circulation with a half-life of approximately 2 minutes, mainly via the liver. It is concluded that PA-inhibitor neutralizes one-chain and two-chain molecular forms of t-PA in plasma at very similar rates, both in vitro and in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)ElsevierDadun. Depósito Académico Digital Universidad de Navarra20122012-07-1919861986-01-0119861986-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/22923reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Universidad de NavarraInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/229232026-06-21T12:47:57Z
dc.title.none.fl_str_mv Inhibition of one-chain and two-chain forms of human tissue-type plasminogen activator by the fast-acting inhibitor of plasminogen activator in vitro and in vivo
title Inhibition of one-chain and two-chain forms of human tissue-type plasminogen activator by the fast-acting inhibitor of plasminogen activator in vitro and in vivo
spellingShingle Inhibition of one-chain and two-chain forms of human tissue-type plasminogen activator by the fast-acting inhibitor of plasminogen activator in vitro and in vivo
Colucci, M. (M.)|||/items/4eda9c08-b77a-450e-b65a-1e4858fda75a
Plasminogen Activators/antagonists & inhibitors
Plasminogen Inactivators
Tissue Plasminogen Activator/antagonists & inhibitors
title_short Inhibition of one-chain and two-chain forms of human tissue-type plasminogen activator by the fast-acting inhibitor of plasminogen activator in vitro and in vivo
title_full Inhibition of one-chain and two-chain forms of human tissue-type plasminogen activator by the fast-acting inhibitor of plasminogen activator in vitro and in vivo
title_fullStr Inhibition of one-chain and two-chain forms of human tissue-type plasminogen activator by the fast-acting inhibitor of plasminogen activator in vitro and in vivo
title_full_unstemmed Inhibition of one-chain and two-chain forms of human tissue-type plasminogen activator by the fast-acting inhibitor of plasminogen activator in vitro and in vivo
title_sort Inhibition of one-chain and two-chain forms of human tissue-type plasminogen activator by the fast-acting inhibitor of plasminogen activator in vitro and in vivo
dc.creator.none.fl_str_mv Colucci, M. (M.)|||/items/4eda9c08-b77a-450e-b65a-1e4858fda75a
Páramo-Fernández, J.A. (José Antonio)|||/items/8c56baa6-2a43-4836-b91b-4eed15be3c96
Collen, D. (D.)|||/items/879361bf-d2c1-4d21-b62e-dd439ac8e527
author Colucci, M. (M.)|||/items/4eda9c08-b77a-450e-b65a-1e4858fda75a
author_facet Colucci, M. (M.)|||/items/4eda9c08-b77a-450e-b65a-1e4858fda75a
Páramo-Fernández, J.A. (José Antonio)|||/items/8c56baa6-2a43-4836-b91b-4eed15be3c96
Collen, D. (D.)|||/items/879361bf-d2c1-4d21-b62e-dd439ac8e527
author_role author
author2 Páramo-Fernández, J.A. (José Antonio)|||/items/8c56baa6-2a43-4836-b91b-4eed15be3c96
Collen, D. (D.)|||/items/879361bf-d2c1-4d21-b62e-dd439ac8e527
author2_role author
author
dc.contributor.none.fl_str_mv Dadun. Depósito Académico Digital Universidad de Navarra
dc.subject.none.fl_str_mv Plasminogen Activators/antagonists & inhibitors
Plasminogen Inactivators
Tissue Plasminogen Activator/antagonists & inhibitors
topic Plasminogen Activators/antagonists & inhibitors
Plasminogen Inactivators
Tissue Plasminogen Activator/antagonists & inhibitors
description The inhibition of one-chain and two-chain molecular forms of human tissue-type plasminogen activator (t-PA) by the fast-acting inhibitor of plasminogen activator (PA-inhibitor) present in plasma was studied in vitro and in vivo in rabbits. In vitro, both one-chain and two-chain forms of t-PA were neutralized very rapidly in rabbit plasma with high levels of PA-inhibitor. The rate constant of the interaction between two-chain t-PA and PA-inhibitor was estimated to be 3.10(7) L/mol/sec. The presence of CNBr-digested fibrinogen, which mimics the effect of fibrin on the activation of plasminogen by t-PA, did not influence the rate constant. Moreover, PA-inhibitor-rich plasma inhibited in a very similar way in vitro thrombolysis by one-chain or two-chain t-PA incorporated into the clot. Injection of one-chain or two-chain t-PA into rabbits with increased levels of PA-inhibitor, induced by endotoxin, resulted in very rapid inhibition of t-PA activity. Within 30 seconds after injection, no residual free t-PA could be demonstrated. Gel filtration analysis showed that the disappearance of t-PA activity was associated with the generation of t-PA-PA-inhibitor complex with an apparent Mr of 100,000. This enzyme-inhibitor complex, like free t-PA, was cleared from the circulation with a half-life of approximately 2 minutes, mainly via the liver. It is concluded that PA-inhibitor neutralizes one-chain and two-chain molecular forms of t-PA in plasma at very similar rates, both in vitro and in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
publishDate 1986
dc.date.none.fl_str_mv 1986
1986-01-01
1986
1986-01-01
2012
2012-07-19
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10171/22923
url https://hdl.handle.net/10171/22923
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra
instname:Universidad de Navarra
instname_str Universidad de Navarra
reponame_str Dadun. Depósito Académico Digital de la Universidad de Navarra
collection Dadun. Depósito Académico Digital de la Universidad de Navarra
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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