Effects of selective and non-selective COX inhibitors on antigen-induced release of prostanoid mediators and bronchoconstriction in the isolated perfused and ventilated guinea pig lung

Prostaglandins Leukot Essent Fatty Acids. 2008 Feb;78(2):89-97. doi: 10.1016/j.plefa.2008.01.001.

Abstract

The contribution of cycloxygenase (COX)-1 and COX-2 in antigen-induced release of mediators and ensuing bronchoconstriction was investigated in the isolated perfused guinea pig lung (IPL). Antigen challenge with ovalbumin (OVA) of lungs from actively sensitised animals induced release of thromboxane (TX)A(2), prostaglandin (PG)D(2), PGF(2)(alpha), PGI(2) and PGE(2), measured in the lung effluent as immunoreactive TXB(2), PGD(2)-MOX, PGF(2)(alpha), 6-keto PGF(1)(alpha) and PGE(2), respectively. This release was abolished by the non-selective COX inhibitor flurbiprofen (10 microM). In contrast, neither the selective COX-1 inhibitor FR122047 nor the selective COX-2 inhibitor celecoxib (10 microM each) significantly inhibited the OVA-induced bronchoconstriction or release of COX products, except for PGD(2). Another non-selective COX inhibitor, diclofenac (10 microM) also significantly inhibited antigen-induced bronchoconstriction. The data suggest that both COX isoenzymes, COX-1 and COX-2 contribute to the immediate antigen-induced generation of prostanoids in IPL and that the COX-1 and COX-2 activities are not associated with different profiles of prostanoid end products.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bronchoconstriction / immunology*
  • Celecoxib
  • Cyclooxygenase 1 / metabolism
  • Cyclooxygenase 2 / metabolism
  • Cyclooxygenase Inhibitors / metabolism*
  • Diclofenac / metabolism
  • Flurbiprofen / metabolism
  • Guinea Pigs
  • Humans
  • Leukotrienes / chemistry
  • Leukotrienes / immunology
  • Lung* / immunology
  • Lung* / physiology
  • Male
  • Ovalbumin / immunology*
  • Piperazines / metabolism
  • Prostaglandins / immunology*
  • Pyrazoles / metabolism
  • Sulfonamides / metabolism
  • Thiazoles / metabolism
  • Thromboxane A2 / immunology
  • Thromboxane B2 / immunology

Substances

  • Cyclooxygenase Inhibitors
  • Leukotrienes
  • Piperazines
  • Prostaglandins
  • Pyrazoles
  • Sulfonamides
  • Thiazoles
  • 1-((4,5-bis(4-methoxyphenyl)-2-thiazoyl)carbonyl)-4-methylpiperazine
  • Diclofenac
  • Thromboxane B2
  • Thromboxane A2
  • Flurbiprofen
  • Ovalbumin
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Celecoxib