Endothelin, PAF and thromboxane A2 in allergic pulmonary hyperreactivity in mice.
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.
Richter
Martin
M
Institute of Pharmacology of Sherbrooke, Medical School, Sherbrooke University, 3001, 12(e) Avenue Nord, Sherbrooke (Qc) Canada J1H 5N4.
Cloutier
Solange
S
Sirois
Pierre
P
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*
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