Endothelin B Receptor Modulates Inflammatory Pain and Cutaneous Inflammation

Abstract

The role of endothelin B (ET_B) receptors in inflammation and nociception was examined using ET_B receptor knockout mice. Genotyping studies were used with tissues from ET_B^(+/+), ET_B^(+/−), and ET_B^(−/−) mice to confirm the loss of ET_B receptors. Algesia induced by phenylbenzoquinone was evident in the (+/+) mice, reduced by ∼80% in the (+/−) mice, and absent in the (−/−) mice. Phenylbenzoquinone-induced algesia in (+/+) mice was inhibited 74% by the ET_B receptor-selective antagonist A192621 (25 mg/kg p.o.), but unaffected by the ET_A receptor-selective antagonist SB 234551 (25 mg/kg p.o.). Noninflammatory pain, induced by hotplate, was equivalent between (+/+) and (−/−) mice. The cutaneous inflammatory response to topical arachidonic acid (AA) also was evaluated. Whereas (+/+) mice had a marked inflammatory response to AA, the (+/−), and (−/−) mice had significantly reduced fluid phase responses (37 and 65% inhibition, respectively). Neutrophil infiltration also was reduced in the (+/−) and (−/−) mice (51 and 65% reduction, respectively). Topical administration of A192621 (500 μg/ear) in (+/+) mice inhibited AA-induced swelling (39%), whereas SB 234551 (500 μg/ear) was without effect. Collectively, these results implicate the ET_B receptor in mediation of inflammatory pain and cutaneous inflammatory responses in mice.