title: Endothelin, PAF and thromboxane A2 in allergic pulmonary hyperreactivity in mice.
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.
authors: Institute of Pharmacology of Sherbrooke, Medical School, Sherbrooke University, 3001, 12(e) Avenue Nord, Sherbrooke (Qc) Canada J1H 5N4.
authors: Martin
authors: M
authors: Richter
authors: Solange
authors: S
authors: Cloutier
authors: Pierre
authors: P
authors: Sirois
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000378:metabolism; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D002217:Carbachol / Q000276:immunology; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism; D016232:Endothelins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009842:Oligopeptides / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000378:metabolism; D010742:Phospholipid Ethers / Q000378:metabolism; D010880:Piperidines / Q000378:metabolism; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010975:Platelet Aggregation Inhibitors / Q000378:metabolism; D011450:Prostaglandin Endoperoxides, Synthetic / Q000378:metabolism; D044023:Receptor, Endothelin B / Q000819:agonists; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000959:Antihypertensive Agents; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1; D016232:Endothelins; D009842:Oligopeptides; D010446:Peptide Fragments; D010742:Phospholipid Ethers; D010880:Piperidines; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D011450:Prostaglandin Endoperoxides, Synthetic; D044023:Receptor, Endothelin B; C074308:sovateltide; C086539:BQ 788; C028429:U 44069; D013928:Thromboxane A2; C037913:CV 3988; D002217:Carbachol; D010047:Ovalbumin