ET(A) 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 mu g/paw) to OVA-sensitized mice [50 mu g 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 f rom 59.6 +/- 4.0 to 48.3 +/- 5.4, 44.6 +/- 3.8, and 34 +/- 2.0 mu l, r espectively (p < 0.05; n = 6). Like BQ-123, FR 139317 (7.5, 75, and 75 0 pmol/paw) also inhibited OVA-induced edema in a graded fashion but w as less potent. In contrast, BQ-123 (150 pmol/paw) failed to affect pa w edema induced in nonsensitized mice by histamine (100 mu g/paw), ser otonin (100 mu g/paw), or zymosan (500 mu g/paw), but significantly re duced edema induced by carrageenan (300 mu g/paw) by 30% (p < 0.05). T hese results strongly suggest that endogenous ETs, acting through ET(A ) receptors, play an important proinflammatory role in the allergic re action to OVA.