Endotoxin-induced hyperreactivity of the guinea-pig isolated trachea coincides with decreased prostaglandin E2production by the epithelial layer

G. Folkerts, F. Engels, F.P. Nijkamp

Research output: Contribution to journalArticleAcademicpeer-review


1. Pretreatment of guinea-pigs with endotoxin (1 mg kg-1b.w., i.p., 4 days before the experiments) results in respiratory airway hyperreactivity in vitro. Dose-response curves with either arecoline or histamine on isolated tracheae from these animals display increased maximal contractions, and decreased EC50values. 2. Tracheae denuded of epithelium respond with a similar hyperreactivity to histamine as observed in preparations from endotoxin pretreated animals. Removal of the epithelial layer of tracheae from endotoxin pretreated guinea-pigs did not additionally affect the histamine dose-response curve. 3. The cyclo-oxygnease inhibitor indomethacin (10 μM) induces histamine hyperreactivity which is equal in intact and epithelium-denuded tracheae from saline or endotoxin pretreated guinea-pigs. Similar results are obtained with the combined lipoxygenase/cyclo-oxygenase inhibitor nordihydroguaiaretic acid (10 μM). 4. Histamine (0.1 mM) induces an increase in prostaglandin E2(PGE2) formation by the tracheal spiral in vitro, which is reduced by 34% by endotoxin pretreatment, and by about 60% following epithelium removal irrespective of endotoxin pretreatment. 5. Arachidonic acid (AA, 22 μM) stimulation of the guinea-pig trachea in vitro induces a relaxation, and an increase in PGE2production. In preparations lacking the epithelium, AA induces a contraction which coincides with a 60% reduced increase in PGE2formation. These effects are not altered by endotoxin pretreatment. 6. It is concluded that the endotoxin-induced respiratory airway hyperreactivity may be caused by a disturbed ability of epithelial cells to synthesize PGE2. The decreased formation of this prostaglandin is rather the consequence of a diminished liberation of AA from the phospholipid stores than a dysfunction of the cyclo-oxygenase enzyme.
Original languageEnglish
Pages (from-to)388-394
Number of pages7
JournalBritish Journal of Pharmacology
Issue number2
Publication statusPublished - 28 Mar 1989


  • 7 [3 (4 acetyl 3 hydroxy 2 propylphenoxy) 2 hydroxypropoxy] 4 oxo 8 propyl 4h 1 benzopyran 2 carboxylic acid
  • arachidonic acid
  • arecoline
  • Escherichia coli endotoxin
  • histamine
  • indometacin
  • nordihydroguaiaretic acid
  • piriprost
  • prostaglandin E2
  • radioisotope
  • animal cell
  • bronchus hyperreactivity
  • dose response
  • epithelium
  • guinea pig
  • male
  • nonhuman
  • priority journal
  • radioimmunoassay
  • trachea


Dive into the research topics of 'Endotoxin-induced hyperreactivity of the guinea-pig isolated trachea coincides with decreased prostaglandin E2production by the epithelial layer'. Together they form a unique fingerprint.

Cite this