Inhibition by thromboxane antagonists of airway hyperresponsiveness to histamine induced by 13,14-dihydro-15-keto-PGF2 alpha in guinea-pigs.

Abstract

We studied the effect of intravenous administration of 13,14-dihydro-15-keto-prostaglandin (PG) F2 alpha on airway responsiveness to histamine and airway wall thickening in guinea-pigs. Guinea-pigs were killed and the lungs were fixed in formalin. Slides from paraffin-embedded sections of the lungs were stained and the airways that were cut in transverse section were measured by tracing enlarged images using a digitizer. Moreover, airway resistance (Raw) was determined by a pulmonary mechanics analyser and we calculated two indices, an index of airway wall thickening and the one of airway hyperresponsiveness to histamine, from changes of baseline-Raw and peak-Raw following intravenous administration of histamine before and after the intravenous administration of 13,14-dihydro-15-keto-PGF2 alpha. Intravenous administration of 10 micrograms/kg 13,14-dihydro-15-keto-PGF2 alpha for 1 h did not induce an increase of the relative thickness of the airway wall by the histological examination. In analysis of airway function, intravenous administration of 10 micrograms/kg 13,14-dihydro-15-keto-PGF2 alpha for 1 h induced airway hyperresponsiveness to histamine without airway wall thickening. Thromboxane A2 (TXA2) receptor antagonists ONO-NT-126 and ONO-8809 inhibited the 13,14-dihydro-15-keto-PGF2 alpha-induced airway hyperresponsiveness to histamine, suggesting that the effect of 13,14-dihydro-15-keto-PGF2 alpha on bronchial hyperresponsiveness is likely to be mediated through TXA2.

• Authors: M Kurosawa, S Yodonawa, H Inamura, H Tsukagoshi
• Journal: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology (Clin Exp Allergy) Vol. 24 Issue 7 Pg. 669-75 (Jul 1994) ISSN: 0954-7894 [Print] England
• PMID: 7953949 (Publication Type: Journal Article)

Chemical References

• Bridged Bicyclo Compounds
• Fatty Acids, Monounsaturated
• ONO 8809
• ONO-NT 126
• 15-keto-13,14-dihydroprostaglandin F2alpha
• Thromboxane A2
• Histamine
• Dinoprost

Topics

• Animals
• Bridged Bicyclo Compounds (pharmacology)
• Bronchi (drug effects, pathology)
• Bronchial Hyperreactivity (chemically induced, drug therapy)
• Bronchoconstriction (drug effects)
• Dinoprost (analogs & derivatives, antagonists & inhibitors, pharmacology)
• Fatty Acids, Monounsaturated (pharmacology)
• Guinea Pigs
• Histamine (pharmacology)
• Infusions, Intravenous
• Male
• Thromboxane A2 (antagonists & inhibitors, physiology)