Endothelin B receptor modulates inflammatory pain and cutaneous inflammation

The role of endothelin B (ETB) receptors in inflammation and nociception wa s examined using ETB receptor knockout mice. Genotyping studies were used w ith tissues from ETB(+/ +), ETB(+/ -), and ETB(-/-) mice to confirm the los s of ETB receptors. Algesia induced by phenylbenzoquinone was evident in th e (+/+) mice, reduced by similar to 80% in the (+/-) mice, and absent in th e (-/-) mice. Phenylbenzoquinone-induced algesia in (+/+) mice was inhibite d 74% by the ETB receptor-selective antagonist A192621 (25 mg/kg p.o.), but unaffected by the ETA 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 arachidoni c acid (AA) also was evaluated. Whereas (+/+) mice had a marked inflammator y response to AA, the (+/-), and (-/-) mice had significantly reduced fluid phase responses (37 and 65% inhibition, respectively). Neutrophil infiltra tion also was reduced in the (+/-) and (-/-) mice (51 and 65% reduction, re spectively). Topical administration of A192621 (500 mu g/ear) in (+/+) mice inhibited AA-induced swelling (39%), whereas SB 234551 (500 mu g/ear) was without effect. Collectively, these results implicate the ETB receptor in m ediation of inflammatory pain and cutaneous inflammatory responses in mice.