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U46619 (a thromboxane A2 mimetic) induces airflow obstruction and airway plasma extravasation in the guinea pig: the role of histamine, cyclooxygenase metabolites, leukotrienes and PAF

Kawikova, I; Arakawa, H; Skoogh, B E; Löfdahl, Claes-Göran LU and Lotvall, J (1996) In Journal of Pharmacology and Experimental Therapeutics 278(1). p.268-276
Abstract
The aim of the present study was to characterize the airway effects of U46619, a stable thromboxane A2 mimetic, instilled into the trachea of guinea pigs in vivo, and to investigate the role of different mediators in these effects. The airflow obstruction was evaluated by measurement of airway insufflation pressure (P1) and plasma extravasation by quantification of Evans Blue dye (EBD) in airways. U46619, given as a single dose to each animal (1 pmol-10 nmol), caused a dose-dependent increase in P1 and extravasation of EBD. The threshold dose required to induce an increase in P1 was 30 times lower than the threshold dose necessary to evoke EBD extravasation. The role of inflammatory mediators was studied when 10 pmol (inducing only the... (More)
The aim of the present study was to characterize the airway effects of U46619, a stable thromboxane A2 mimetic, instilled into the trachea of guinea pigs in vivo, and to investigate the role of different mediators in these effects. The airflow obstruction was evaluated by measurement of airway insufflation pressure (P1) and plasma extravasation by quantification of Evans Blue dye (EBD) in airways. U46619, given as a single dose to each animal (1 pmol-10 nmol), caused a dose-dependent increase in P1 and extravasation of EBD. The threshold dose required to induce an increase in P1 was 30 times lower than the threshold dose necessary to evoke EBD extravasation. The role of inflammatory mediators was studied when 10 pmol (inducing only the increase in P1) or 10 nmol (inducing the increase in both P1 and EBD extravasation) of U46619 was administered. The effects of both doses of U46619 were abolished by ICI192,605, an antagonist of prostanoid receptor for thromboxane A2 (0.5 mg/kg i.v.). The airflow obstruction induced by 10 nmol of U46619 was potentiated by indomethacin, a cyclo-oxygenase inhibitor (10 mg/kg i.v.). EBD extravasation induced by 10 nmol U46619 was attenuated by BW70C (6 mg/kg i.v.), a selective 5-lipoxygenase inhibitor, by ICI198,615 (0.5 microgram/kg i.v.), a leukotriene D4/E4 receptor antagonist and by WEB2086 (1 mg/kg i.v.) a platelet-activating factor receptor antagonist. Pyrilamine (2 mg/kg i.v.), a histamine H1 receptor antagonist, did not have any influence on U46619-induced airway effects. We conclude that U46619 possesses a higher potency in the induction of airflow obstruction than in the induction of plasma extravasation and that U46619-induced plasma extravasation may be partly mediated via leukotrienes and platelet-activating factor. (Less)
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author
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Pharmacology and Experimental Therapeutics
volume
278
issue
1
pages
268 - 276
publisher
American Society for Pharmacology and Experimental Therapeutics
external identifiers
  • pmid:8764360
  • scopus:0030302495
ISSN
1521-0103
language
English
LU publication?
no
id
d69173db-9180-4395-8614-5dd71b3a01f2 (old id 1110634)
date added to LUP
2008-07-25 13:53:19
date last changed
2017-01-01 06:41:50
@article{d69173db-9180-4395-8614-5dd71b3a01f2,
  abstract     = {The aim of the present study was to characterize the airway effects of U46619, a stable thromboxane A2 mimetic, instilled into the trachea of guinea pigs in vivo, and to investigate the role of different mediators in these effects. The airflow obstruction was evaluated by measurement of airway insufflation pressure (P1) and plasma extravasation by quantification of Evans Blue dye (EBD) in airways. U46619, given as a single dose to each animal (1 pmol-10 nmol), caused a dose-dependent increase in P1 and extravasation of EBD. The threshold dose required to induce an increase in P1 was 30 times lower than the threshold dose necessary to evoke EBD extravasation. The role of inflammatory mediators was studied when 10 pmol (inducing only the increase in P1) or 10 nmol (inducing the increase in both P1 and EBD extravasation) of U46619 was administered. The effects of both doses of U46619 were abolished by ICI192,605, an antagonist of prostanoid receptor for thromboxane A2 (0.5 mg/kg i.v.). The airflow obstruction induced by 10 nmol of U46619 was potentiated by indomethacin, a cyclo-oxygenase inhibitor (10 mg/kg i.v.). EBD extravasation induced by 10 nmol U46619 was attenuated by BW70C (6 mg/kg i.v.), a selective 5-lipoxygenase inhibitor, by ICI198,615 (0.5 microgram/kg i.v.), a leukotriene D4/E4 receptor antagonist and by WEB2086 (1 mg/kg i.v.) a platelet-activating factor receptor antagonist. Pyrilamine (2 mg/kg i.v.), a histamine H1 receptor antagonist, did not have any influence on U46619-induced airway effects. We conclude that U46619 possesses a higher potency in the induction of airflow obstruction than in the induction of plasma extravasation and that U46619-induced plasma extravasation may be partly mediated via leukotrienes and platelet-activating factor.},
  author       = {Kawikova, I and Arakawa, H and Skoogh, B E and Löfdahl, Claes-Göran and Lotvall, J},
  issn         = {1521-0103},
  language     = {eng},
  number       = {1},
  pages        = {268--276},
  publisher    = {American Society for Pharmacology and Experimental Therapeutics},
  series       = {Journal of Pharmacology and Experimental Therapeutics},
  title        = {U46619 (a thromboxane A2 mimetic) induces airflow obstruction and airway plasma extravasation in the guinea pig: the role of histamine, cyclooxygenase metabolites, leukotrienes and PAF},
  volume       = {278},
  year         = {1996},
}