ETA receptor antagonists inhibit allergic inflammation in the mouse.
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.
Sampaio
A L
AL
Department of Physiology and Pharmacodynamics, I.O.C. Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
Rae
G A
GA
D'Orléans-Juste
P
P
Henriques
M G
MG
D000818:Animals; D001381:Azepines / Q000627:therapeutic use*; D004487:Edema / Q000209:etiology / Q000517:prevention & control*; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000502:physiology; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D010047:Ovalbumin / Q000276:immunology; D010456:Peptides, Cyclic / Q000627:therapeutic use*; D044022:Receptor, Endothelin A
D001381:Azepines; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D007211:Indoles; D010456:Peptides, Cyclic; D044022:Receptor, Endothelin A; C079574:FR 139317; D010047:Ovalbumin; C072247:cyclo(Trp-Asp-Pro-Val-Leu)