ETA receptor antagonists inhibit allergic inflammation in the mouse.

Abstract

This study investigated the influence of the selective endothelin (ET) ETA receptor antagonists BQ-123 and FR 139317 on paw edema induced by ovalbumin (OVA) injection (3 micrograms/paw) to OVA-sensitized mice [50 micrograms in 5 mg of Al(OH)3, s.c., 14 days earlier]. Injections of BQ-123 (1.5, 15, and 150 pmol/paw, 15 min earlier) reduced OVA-induced edema from 59.6 +/- 4.0 to 48.3 +/- 5.4, 44.6 +/- 3.8, and 34 +/- 2.0 microliters, respectively (p < 0.05; n = 6). Like BQ-123, FR 139317 (7.5, 75, and 750 pmol/paw) also inhibited OVA-induced edema in a graded fashion but was less potent. In contrast, BQ-123 (150 pmol/paw) failed to affect paw edema induced in nonsensitized mice by histamine (100 micrograms/paw), serotonin (100 micrograms/paw), or zymosan (500 micrograms/paw), but significantly reduced edema induced by carrageenan (300 micrograms/paw) by 30% (p < 0.05). These results strongly suggest that endogenous ETs, acting through ETA receptors, play an important proinflammatory role in the allergic reaction to OVA.

• Authors: A L Sampaio, G A Rae, P D'Orléans-Juste, M G Henriques
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 26 Suppl 3 Pg. S416-8 ( 1995) ISSN: 0160-2446 [Print] United States
• PMID: 8587431 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Azepines
• Endothelin Receptor Antagonists
• Endothelins
• Indoles
• Peptides, Cyclic
• Receptor, Endothelin A
• FR 139317
• Ovalbumin
• cyclo(Trp-Asp-Pro-Val-Leu)

Topics

• Animals
• Azepines (therapeutic use)
• Edema (etiology, prevention & control)
• Endothelin Receptor Antagonists
• Endothelins (physiology)
• Indoles (therapeutic use)
• Male
• Mice
• Ovalbumin (immunology)
• Peptides, Cyclic (therapeutic use)
• Receptor, Endothelin A