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Effects of OKY 1581 on bronchoconstrictor responses to arachidonic acid and PGH2.
J Appl Physiol (1985). 1987 May; 62(5):2066-74.JA

Abstract

The influence of OKY 1581, a thromboxane synthase inhibitor, on airway responses to arachidonic acid and endoperoxide, [prostaglandin (PG) H2], were investigated in anesthetized, paralyzed, mechanically ventilated cats. Intravenous injections of arachidonic acid and PGH2 caused dose-related increases in transpulmonary pressure and lung resistance and decreases in dynamic and static compliance. OKY 1581 significantly decreased airway responses to arachidonic acid but not to PGH2. Sodium meclofenamate, a cyclooxygenase inhibitor, abolished airway responses to arachidonic acid but had no effect on airway responses to PGH2. OKY 1581 or meclofenamate has no effect on airway responses to PGF2 alpha, PGD2, or U 46619, a thromboxane mimic. In microsomal fractions from the lung, OKY 1581 inhibited thromboxane formation without decreasing prostacyclin synthesis or cyclooxygenase activity. These studies show that OKY 1581 is a selective thromboxane synthesis inhibitor in the cat lung and suggest that a substantial part of the bronchoconstrictor response to arachidonic acid is due to thromboxane A2 formation. Moreover, the present data suggest that airway responses to endogenously released and exogenous PGH2 are mediated differently and that a significant part of the response to exogenous PGH2 may be due to activation of an endoperoxide/thromboxane receptor, since responses to PGH2 are blocked by the thromboxane receptor antagonist SQ 29548.

Authors

No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

2954941

Citation

Tilden, S J., et al. "Effects of OKY 1581 On Bronchoconstrictor Responses to Arachidonic Acid and PGH2." Journal of Applied Physiology (Bethesda, Md. : 1985), vol. 62, no. 5, 1987, pp. 2066-74.
Tilden SJ, Underwood DC, Cowen KH, et al. Effects of OKY 1581 on bronchoconstrictor responses to arachidonic acid and PGH2. J Appl Physiol (1985). 1987;62(5):2066-74.
Tilden, S. J., Underwood, D. C., Cowen, K. H., Wegmann, M. J., Graybar, G. B., Hyman, A. L., McNamara, D. B., & Kadowitz, P. J. (1987). Effects of OKY 1581 on bronchoconstrictor responses to arachidonic acid and PGH2. Journal of Applied Physiology (Bethesda, Md. : 1985), 62(5), 2066-74.
Tilden SJ, et al. Effects of OKY 1581 On Bronchoconstrictor Responses to Arachidonic Acid and PGH2. J Appl Physiol (1985). 1987;62(5):2066-74. PubMed PMID: 2954941.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of OKY 1581 on bronchoconstrictor responses to arachidonic acid and PGH2. AU - Tilden,S J, AU - Underwood,D C, AU - Cowen,K H, AU - Wegmann,M J, AU - Graybar,G B, AU - Hyman,A L, AU - McNamara,D B, AU - Kadowitz,P J, PY - 1987/5/1/pubmed PY - 1987/5/1/medline PY - 1987/5/1/entrez SP - 2066 EP - 74 JF - Journal of applied physiology (Bethesda, Md. : 1985) JO - J Appl Physiol (1985) VL - 62 IS - 5 N2 - The influence of OKY 1581, a thromboxane synthase inhibitor, on airway responses to arachidonic acid and endoperoxide, [prostaglandin (PG) H2], were investigated in anesthetized, paralyzed, mechanically ventilated cats. Intravenous injections of arachidonic acid and PGH2 caused dose-related increases in transpulmonary pressure and lung resistance and decreases in dynamic and static compliance. OKY 1581 significantly decreased airway responses to arachidonic acid but not to PGH2. Sodium meclofenamate, a cyclooxygenase inhibitor, abolished airway responses to arachidonic acid but had no effect on airway responses to PGH2. OKY 1581 or meclofenamate has no effect on airway responses to PGF2 alpha, PGD2, or U 46619, a thromboxane mimic. In microsomal fractions from the lung, OKY 1581 inhibited thromboxane formation without decreasing prostacyclin synthesis or cyclooxygenase activity. These studies show that OKY 1581 is a selective thromboxane synthesis inhibitor in the cat lung and suggest that a substantial part of the bronchoconstrictor response to arachidonic acid is due to thromboxane A2 formation. Moreover, the present data suggest that airway responses to endogenously released and exogenous PGH2 are mediated differently and that a significant part of the response to exogenous PGH2 may be due to activation of an endoperoxide/thromboxane receptor, since responses to PGH2 are blocked by the thromboxane receptor antagonist SQ 29548. SN - 8750-7587 UR - https://www.unboundmedicine.com/medline/citation/2954941/Effects_of_OKY_1581_on_bronchoconstrictor_responses_to_arachidonic_acid_and_PGH2_ L2 - https://journals.physiology.org/doi/10.1152/jappl.1987.62.5.2066?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -