Hyperalgesia induced by Asp49 and Lys49 phospholipases A2 from Bothrops asper snake venom: pharmacological mediation and molecular determinants

The ability of Lys49 and Asp49 phospholipases A2 (PLA2), from Bothrops asper snake venom, to cause hyperalgesia was investigated in rats, using the paw pressure test. Intraplantar injection of both toxins (5–20 μg/paw) caused hyperalgesia, which peaked 1 h after injections. Incubation of both protei...

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Autores: Chacur, Marucia, Longo, I., Picolo, Gisele, Gutiérrez, José María, Lomonte, Bruno, Guerra, J. L., Teixeira, Catarina de Fátima, Cury, Yara
Formato: artículo
Fecha de publicación:2003
País:Costa Rica
Recursos:Universidad de Costa Rica
Repositorio:Kérwá
OAI Identifier:oai:kerwa.ucr.ac.cr:10669/29490
Acesso em linha:http://www.sciencedirect.com/science/article/pii/S0041010103000072
https://hdl.handle.net/10669/29490
Access Level:acceso embargado
Palavra-chave:Hyperalgesia
Phospholipases A2
Biogenic Amines
Bradykinin
Cytokines
Prostanoids
Sympathomimetic Amines
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dc.title.es_ES.fl_str_mv Hyperalgesia induced by Asp49 and Lys49 phospholipases A2 from Bothrops asper snake venom: pharmacological mediation and molecular determinants
title Hyperalgesia induced by Asp49 and Lys49 phospholipases A2 from Bothrops asper snake venom: pharmacological mediation and molecular determinants
spellingShingle Hyperalgesia induced by Asp49 and Lys49 phospholipases A2 from Bothrops asper snake venom: pharmacological mediation and molecular determinants
Chacur, Marucia
Hyperalgesia
Phospholipases A2
Biogenic Amines
Bradykinin
Cytokines
Prostanoids
Sympathomimetic Amines
title_short Hyperalgesia induced by Asp49 and Lys49 phospholipases A2 from Bothrops asper snake venom: pharmacological mediation and molecular determinants
title_full Hyperalgesia induced by Asp49 and Lys49 phospholipases A2 from Bothrops asper snake venom: pharmacological mediation and molecular determinants
title_fullStr Hyperalgesia induced by Asp49 and Lys49 phospholipases A2 from Bothrops asper snake venom: pharmacological mediation and molecular determinants
title_full_unstemmed Hyperalgesia induced by Asp49 and Lys49 phospholipases A2 from Bothrops asper snake venom: pharmacological mediation and molecular determinants
title_sort Hyperalgesia induced by Asp49 and Lys49 phospholipases A2 from Bothrops asper snake venom: pharmacological mediation and molecular determinants
dc.creator.none.fl_str_mv Chacur, Marucia
Longo, I.
Picolo, Gisele
Gutiérrez, José María
Lomonte, Bruno
Guerra, J. L.
Teixeira, Catarina de Fátima
Cury, Yara
author Chacur, Marucia
author_facet Chacur, Marucia
Longo, I.
Picolo, Gisele
Gutiérrez, José María
Lomonte, Bruno
Guerra, J. L.
Teixeira, Catarina de Fátima
Cury, Yara
author_role author
author2 Longo, I.
Picolo, Gisele
Gutiérrez, José María
Lomonte, Bruno
Guerra, J. L.
Teixeira, Catarina de Fátima
Cury, Yara
author2_role author
author
author
author
author
author
author
dc.subject.es_ES.fl_str_mv Hyperalgesia
Phospholipases A2
Biogenic Amines
Bradykinin
Cytokines
Prostanoids
Sympathomimetic Amines
topic Hyperalgesia
Phospholipases A2
Biogenic Amines
Bradykinin
Cytokines
Prostanoids
Sympathomimetic Amines
description The ability of Lys49 and Asp49 phospholipases A2 (PLA2), from Bothrops asper snake venom, to cause hyperalgesia was investigated in rats, using the paw pressure test. Intraplantar injection of both toxins (5–20 μg/paw) caused hyperalgesia, which peaked 1 h after injections. Incubation of both proteins with heparin, prior to their injection, partially reduced this response. Chemical modification of Asp49 PLA2 with p-bromophenacyl bromide (p-BPB), which abrogates its PLA2 activity, also abolished hyperalgesia. Intraplantar injection of a synthetic peptide corresponding to the C-terminal sequence 115–129 of Lys49 PLA2, caused hyperalgesia of similar time course, but varying magnitude, than that induced by the native protein. In contrast, a homologous peptide derived from the Asp49 PLA2 did not show any nociceptive effect. Hyperalgesia induced by both PLA2s was blocked by the histamine and serotonin receptor antagonists promethazine and methysergide, respectively, by the bradykinin B2 receptor antagonist HOE 140 and by antibodies to tumor necrosis factor alfa (TNFα) and interleukin 1 (IL-1). Pretreatment with guanethidine, atenolol, prazosin and yohimbine, inhibitors of sympathomimetic amines, or with indomethacin, inhibitor of the cyclo-oxygenase pathway, reduced Lys49 PLA2-induced hyperalgesia without interfering with the nociceptive activity of Asp49 PLA2. The hyperalgesic response to both myotoxins was not modified by pretreatment with celecoxib, an inhibitor of the cyclo-oxygenase type II, by zileuton, an inhibitor of the lipoxygenase pathway or by Ng-methyl-l-arginine (LNMMA), an inhibitor of nitric oxide synthase. These results suggest that Asp49 and Lys49 PLA2s are important hyperalgesic components of B. asper venom, and that Lys49 and Asp49 PLA2s exert their algogenic actions through different molecular mechanisms.
publishDate 2003
dc.date.issued.none.fl_str_mv 2003-05
dc.date.accessioned.none.fl_str_mv 2017-02-03T19:55:48Z
dc.date.available.none.fl_str_mv 2017-02-03T19:55:48Z
dc.type.none.fl_str_mv artículo original
http://purl.org/coar/resource_type/c_2df8fbb1
info:eu-repo/semantics/article
format article
dc.identifier.citation.none.fl_str_mv http://www.sciencedirect.com/science/article/pii/S0041010103000072
dc.identifier.issn.none.fl_str_mv 0041-0101
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/10669/29490
dc.identifier.doi.none.fl_str_mv 10.1016/S0041-0101(03)00007-2
dc.identifier.pmid.none.fl_str_mv 12727271
url http://www.sciencedirect.com/science/article/pii/S0041010103000072
https://hdl.handle.net/10669/29490
identifier_str_mv 0041-0101
10.1016/S0041-0101(03)00007-2
12727271
dc.language.iso.es_ES.fl_str_mv en_US
language_invalid_str_mv en_US
dc.rights.none.fl_str_mv acceso embargado
http://purl.org/coar/access_right/c_f1cf
info:eu-repo/semantics/embargoedAccess
rights_invalid_str_mv acceso embargado
http://purl.org/coar/access_right/c_f1cf
eu_rights_str_mv embargoedAccess
dc.source.es_ES.fl_str_mv Toxicon; Volumen 41, Número 6, 2003
dc.source.none.fl_str_mv reponame:Kérwá
instname:Universidad de Costa Rica
instacron:UCR
instname_str Universidad de Costa Rica
instacron_str UCR
institution UCR
reponame_str Kérwá
collection Kérwá
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repository.name.fl_str_mv Kérwá - Universidad de Costa Rica
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Incubation of both proteins with heparin, prior to their injection, partially reduced this response. Chemical modification of Asp49 PLA2 with p-bromophenacyl bromide (p-BPB), which abrogates its PLA2 activity, also abolished hyperalgesia. Intraplantar injection of a synthetic peptide corresponding to the C-terminal sequence 115–129 of Lys49 PLA2, caused hyperalgesia of similar time course, but varying magnitude, than that induced by the native protein. In contrast, a homologous peptide derived from the Asp49 PLA2 did not show any nociceptive effect. Hyperalgesia induced by both PLA2s was blocked by the histamine and serotonin receptor antagonists promethazine and methysergide, respectively, by the bradykinin B2 receptor antagonist HOE 140 and by antibodies to tumor necrosis factor alfa (TNFα) and interleukin 1 (IL-1). Pretreatment with guanethidine, atenolol, prazosin and yohimbine, inhibitors of sympathomimetic amines, or with indomethacin, inhibitor of the cyclo-oxygenase pathway, reduced Lys49 PLA2-induced hyperalgesia without interfering with the nociceptive activity of Asp49 PLA2. The hyperalgesic response to both myotoxins was not modified by pretreatment with celecoxib, an inhibitor of the cyclo-oxygenase type II, by zileuton, an inhibitor of the lipoxygenase pathway or by Ng-methyl-l-arginine (LNMMA), an inhibitor of nitric oxide synthase. 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