Prostaglandins, Leukotrienes and Essential Fatty Acids (PLEFA) 2007-05-01

Endothelin, PAF and thromboxane A2 in allergic pulmonary hyperreactivity in mice.

Martin Richter, Solange Cloutier, Pierre Sirois

Index: Prostaglandins Leukot. Essent. Fatty Acids 76(5) , 299-308, (2007)

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Abstract

The role of endothelin, PAF and thromboxane A2 in airway hyperreactivity (AHR) to carbachol induced by ovalbumin sensitization and challenge in Balb/c mice was investigated. Ovalbumin sensitization and challenge induced significant AHR to carbachol in actively sensitized and challenged mice. Treatment of these mice with the PAF antagonist CV-3988 (10 microg kg(-1), i.v.) completely abolished OVA-induced AHR to carbachol. Treatment of sensitized mice with the TxA2 antagonist L-654,664 (1 mg kg(-1), i.v.) partially blocked the induction of AHR in OVA-challenged mice. The intranasal administration of 50 pmol of the ET(A) receptor antagonist BQ-123 had no effect on the PIP but produced a significant reduction at the dose of 100 pmol. The intravenous administration of BQ-123 (100 pmol) reduced the PIP only at the highest doses of carbachol. The ET(B) receptor antagonist BQ-788 administered either via the intranasal or intravenous route had no effect on the PIP at the dose of 100 pmol. Naïve mice treated with either U-44069 (25 or 100 microg kg(-1), i.v.), endothelin-1 (100 pmol, intranasally) or the ET(B) receptor agonist IRL-1620 (100 pmol, intranasally) showed a marked increase in airway reactivity to carbachol. These results suggest an important role for endothelin, PAF and thromboxane A2 in AHR in mice actively sensitized and challenged with ovalbumin.