Cargando…

Calcium ionophore (A-23187) induced peritoneal eicosanoid biosynthesis: a rapid method to evaluate inhibitors of arachidonic acid metabolism in vivo

The present investigation characterizes calcium ionophore (A-23187) induced peritoneal eicosanoid biosynthesis in the rat. Intraperitoneal injection of A-23187 (20 μg/rat) stimulated marked biosynthesis of 6-keto-PGF(1α) (6-KPA), TxB(2), LTC(4) and LTB(4), with no detectable changes on levels of PGE...

Descripción completa

Detalles Bibliográficos
Autores principales: Rao, T. S., Currie, J. L., Shaffer, A. F., Isakson, P. C.
Formato: Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 1993
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2365427/
https://www.ncbi.nlm.nih.gov/pubmed/18475545
http://dx.doi.org/10.1155/S0962935193000493
_version_ 1782154165891366912
author Rao, T. S.
Currie, J. L.
Shaffer, A. F.
Isakson, P. C.
author_facet Rao, T. S.
Currie, J. L.
Shaffer, A. F.
Isakson, P. C.
author_sort Rao, T. S.
collection PubMed
description The present investigation characterizes calcium ionophore (A-23187) induced peritoneal eicosanoid biosynthesis in the rat. Intraperitoneal injection of A-23187 (20 μg/rat) stimulated marked biosynthesis of 6-keto-PGF(1α) (6-KPA), TxB(2), LTC(4) and LTB(4), with no detectable changes on levels of PGE(2). Levels of all eicosanoids decreased rapidly after a peak which was seen as early as 5 min. Enzyme markers of cellular contents of neutrophils and mononuclear cells, MPO and NAG respectively, decreased rapidly after ionophore injection; this was followed by increases after 60 min. Indomethacin, a selective cyclooxygenase inhibitor, and zileuton and ICI D-2138, two selective 5-lipoxygenase inhibitors attenuated prostaglandin and leukotriene pathways respectively. Oral administration of zileuton (20 mg/kg, p.o.) inhibited LTB(4) biosynthesis for up to 6 h suggesting a long duration of pharmacological activity in the rats consistent with its longer half-life. The rapid onset and the magnitude of increases in levels of eicosanoids render the ionophore induced peritoneal eicosanoid biosynthesis a useful model to evaluate pharmacological profiles of inhibitors of eicosanoid pathways in vivo.
format Text
id pubmed-2365427
institution National Center for Biotechnology Information
language English
publishDate 1993
publisher Hindawi Publishing Corporation
record_format MEDLINE/PubMed
spelling pubmed-23654272008-05-12 Calcium ionophore (A-23187) induced peritoneal eicosanoid biosynthesis: a rapid method to evaluate inhibitors of arachidonic acid metabolism in vivo Rao, T. S. Currie, J. L. Shaffer, A. F. Isakson, P. C. Mediators Inflamm Research Article The present investigation characterizes calcium ionophore (A-23187) induced peritoneal eicosanoid biosynthesis in the rat. Intraperitoneal injection of A-23187 (20 μg/rat) stimulated marked biosynthesis of 6-keto-PGF(1α) (6-KPA), TxB(2), LTC(4) and LTB(4), with no detectable changes on levels of PGE(2). Levels of all eicosanoids decreased rapidly after a peak which was seen as early as 5 min. Enzyme markers of cellular contents of neutrophils and mononuclear cells, MPO and NAG respectively, decreased rapidly after ionophore injection; this was followed by increases after 60 min. Indomethacin, a selective cyclooxygenase inhibitor, and zileuton and ICI D-2138, two selective 5-lipoxygenase inhibitors attenuated prostaglandin and leukotriene pathways respectively. Oral administration of zileuton (20 mg/kg, p.o.) inhibited LTB(4) biosynthesis for up to 6 h suggesting a long duration of pharmacological activity in the rats consistent with its longer half-life. The rapid onset and the magnitude of increases in levels of eicosanoids render the ionophore induced peritoneal eicosanoid biosynthesis a useful model to evaluate pharmacological profiles of inhibitors of eicosanoid pathways in vivo. Hindawi Publishing Corporation 1993 /pmc/articles/PMC2365427/ /pubmed/18475545 http://dx.doi.org/10.1155/S0962935193000493 Text en Copyright © 1993 Hindawi Publishing Corporation. http://creativecommons.org/licenses/by/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Rao, T. S.
Currie, J. L.
Shaffer, A. F.
Isakson, P. C.
Calcium ionophore (A-23187) induced peritoneal eicosanoid biosynthesis: a rapid method to evaluate inhibitors of arachidonic acid metabolism in vivo
title Calcium ionophore (A-23187) induced peritoneal eicosanoid biosynthesis: a rapid method to evaluate inhibitors of arachidonic acid metabolism in vivo
title_full Calcium ionophore (A-23187) induced peritoneal eicosanoid biosynthesis: a rapid method to evaluate inhibitors of arachidonic acid metabolism in vivo
title_fullStr Calcium ionophore (A-23187) induced peritoneal eicosanoid biosynthesis: a rapid method to evaluate inhibitors of arachidonic acid metabolism in vivo
title_full_unstemmed Calcium ionophore (A-23187) induced peritoneal eicosanoid biosynthesis: a rapid method to evaluate inhibitors of arachidonic acid metabolism in vivo
title_short Calcium ionophore (A-23187) induced peritoneal eicosanoid biosynthesis: a rapid method to evaluate inhibitors of arachidonic acid metabolism in vivo
title_sort calcium ionophore (a-23187) induced peritoneal eicosanoid biosynthesis: a rapid method to evaluate inhibitors of arachidonic acid metabolism in vivo
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2365427/
https://www.ncbi.nlm.nih.gov/pubmed/18475545
http://dx.doi.org/10.1155/S0962935193000493
work_keys_str_mv AT raots calciumionophorea23187inducedperitonealeicosanoidbiosynthesisarapidmethodtoevaluateinhibitorsofarachidonicacidmetabolisminvivo
AT curriejl calciumionophorea23187inducedperitonealeicosanoidbiosynthesisarapidmethodtoevaluateinhibitorsofarachidonicacidmetabolisminvivo
AT shafferaf calciumionophorea23187inducedperitonealeicosanoidbiosynthesisarapidmethodtoevaluateinhibitorsofarachidonicacidmetabolisminvivo
AT isaksonpc calciumionophorea23187inducedperitonealeicosanoidbiosynthesisarapidmethodtoevaluateinhibitorsofarachidonicacidmetabolisminvivo