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Leukotriene D4- and prostaglandin F2 alpha-induced airflow obstruction and airway plasma exudation in guinea-pig: role of thromboxane and its receptor

Arakawa, Hirokazu; Lotvall, Jan; Kawikova, Ivana; Löfdahl, Claes-Göran LU and Skoogh, Bengt-Eric (1993) In British Journal of Pharmacology 110(1). p.127-132
Abstract
1 We studied the effects of a thromboxane A2 receptor (TP receptor) antagonist, ICI-192,605 (0.5mgkg-', i.v.) and a selective thromboxane (Tx) synthetase inhibitor, OKY-046 (30mgkg-1, i.v.), on airway responses induced by leukotriene D4 (LTD4; 0.2 nmol) or prostaglandin F2a, (PGF2,; 20 nmol) instilled via the airways route to anaesthetized guinea-pigs. For a comparison, airway responses to a TxA2-mimetic, U-46619 (0.02 nmol) were also studied. We measured both lung resistance (RL) to

monitor airflow obstruction, and extravasation of Evans Blue dye to quantify airway plasma exudation.

2 Instilled LTD4 into the tracheal lumen induced an immediate peak and subsequently persistent increase in RL and produced a large amount of... (More)
1 We studied the effects of a thromboxane A2 receptor (TP receptor) antagonist, ICI-192,605 (0.5mgkg-', i.v.) and a selective thromboxane (Tx) synthetase inhibitor, OKY-046 (30mgkg-1, i.v.), on airway responses induced by leukotriene D4 (LTD4; 0.2 nmol) or prostaglandin F2a, (PGF2,; 20 nmol) instilled via the airways route to anaesthetized guinea-pigs. For a comparison, airway responses to a TxA2-mimetic, U-46619 (0.02 nmol) were also studied. We measured both lung resistance (RL) to

monitor airflow obstruction, and extravasation of Evans Blue dye to quantify airway plasma exudation.

2 Instilled LTD4 into the tracheal lumen induced an immediate peak and subsequently persistent increase in RL and produced a large amount of extravasation of Evans Blue dye at all airway levels. Both ICI-192,605 and OKY-046 significantly attenuated the persistent increase in RL following the immediate response and reduced LTD4-induced extravasation of Evans Blue dye in the trachea and

proximal intrapulmonary airway. Instilled LTD4 produced significant increases in immunoreactive TxB2 in bronchoalveolar lavage fluid obtained 1.5 min after instillation of LTD4.

3 Instilled PGF2. into the tracheal lumen induced an immediate increase in RL which peaked at approximately 15 s. We also observed a delayed sustained increase in RL, reaching a second peak at approximately 4 min. PGF2, produced small but significant increases in the amount of Evans Blue dye at all airway levels. As with PGF,, instillation of U-46619 produced a biphasic increase in RL and extravasation of Evans Blue dye. The potency of PGFu, in inducing these airway responses was about 1000 times less than U-46619. ICI-192,605 abolished both the immediate and the delayed increase in RL after PGF20, and also blocked PGF2,-induced extravasation of Evans Blue dye. However, OKY-046 had no inhibitory effects on these responses.

4 We conclude that airflow obstruction and airway plasma exudation induced by instilled LTD4 is, in part, mediated via TxA2 generation and subsequent activation of TP-receptors. On the other hand, instilled PGF2., while inducing similar responses, does so primarily by direct activation of TP receptors, rather than via TxA2 generation. (Less)
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author
publishing date
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Contribution to journal
publication status
published
subject
keywords
Asthma, airway oedema, arachidonic acid, vascular permeability
in
British Journal of Pharmacology
volume
110
issue
1
pages
127 - 132
publisher
The British Pharmacological Society
external identifiers
  • pmid:8220872
ISSN
1476-5381
language
English
LU publication?
no
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841058ee-cea8-4b9b-bcdc-0ac9dfd85561 (old id 1107404)
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http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2176029
date added to LUP
2008-07-30 17:31:24
date last changed
2016-06-29 09:14:04
@article{841058ee-cea8-4b9b-bcdc-0ac9dfd85561,
  abstract     = {1 We studied the effects of a thromboxane A2 receptor (TP receptor) antagonist, ICI-192,605 (0.5mgkg-', i.v.) and a selective thromboxane (Tx) synthetase inhibitor, OKY-046 (30mgkg-1, i.v.), on airway responses induced by leukotriene D4 (LTD4; 0.2 nmol) or prostaglandin F2a, (PGF2,; 20 nmol) instilled via the airways route to anaesthetized guinea-pigs. For a comparison, airway responses to a TxA2-mimetic, U-46619 (0.02 nmol) were also studied. We measured both lung resistance (RL) to<br/><br>
monitor airflow obstruction, and extravasation of Evans Blue dye to quantify airway plasma exudation.<br/><br>
2 Instilled LTD4 into the tracheal lumen induced an immediate peak and subsequently persistent increase in RL and produced a large amount of extravasation of Evans Blue dye at all airway levels. Both ICI-192,605 and OKY-046 significantly attenuated the persistent increase in RL following the immediate response and reduced LTD4-induced extravasation of Evans Blue dye in the trachea and<br/><br>
proximal intrapulmonary airway. Instilled LTD4 produced significant increases in immunoreactive TxB2 in bronchoalveolar lavage fluid obtained 1.5 min after instillation of LTD4. <br/><br>
3 Instilled PGF2. into the tracheal lumen induced an immediate increase in RL which peaked at approximately 15 s. We also observed a delayed sustained increase in RL, reaching a second peak at approximately 4 min. PGF2, produced small but significant increases in the amount of Evans Blue dye at all airway levels. As with PGF,, instillation of U-46619 produced a biphasic increase in RL and extravasation of Evans Blue dye. The potency of PGFu, in inducing these airway responses was about 1000 times less than U-46619. ICI-192,605 abolished both the immediate and the delayed increase in RL after PGF20, and also blocked PGF2,-induced extravasation of Evans Blue dye. However, OKY-046 had no inhibitory effects on these responses.<br/><br>
4 We conclude that airflow obstruction and airway plasma exudation induced by instilled LTD4 is, in part, mediated via TxA2 generation and subsequent activation of TP-receptors. On the other hand, instilled PGF2., while inducing similar responses, does so primarily by direct activation of TP receptors, rather than via TxA2 generation.},
  author       = {Arakawa, Hirokazu and Lotvall, Jan and Kawikova, Ivana and Löfdahl, Claes-Göran and Skoogh, Bengt-Eric},
  issn         = {1476-5381},
  keyword      = {Asthma,airway oedema,arachidonic acid,vascular permeability},
  language     = {eng},
  number       = {1},
  pages        = {127--132},
  publisher    = {The British Pharmacological Society},
  series       = {British Journal of Pharmacology},
  title        = {Leukotriene D4- and prostaglandin F2 alpha-induced airflow obstruction and airway plasma exudation in guinea-pig: role of thromboxane and its receptor},
  volume       = {110},
  year         = {1993},
}