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 approximately 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 microg/ear) in (+/+) mice inhibited AA-induced swelling (39%), whereas SB 234551 (500 microg/ear) was without effect. Collectively, these results implicate the ET(B) receptor in mediation of inflammatory pain and cutaneous inflammatory responses in mice.

• Authors: D E Griswold, S A Douglas, L D Martin, T G Davis, L Davis, Z Ao, M A Luttmann, M Pullen, P Nambi, D W Hay, E H Ohlstein
• Journal: Molecular pharmacology (Mol Pharmacol) Vol. 56 Issue 4 Pg. 807-12 (Oct 1999) ISSN: 0026-895X [Print] United States
• PMID: 10496965 (Publication Type: Journal Article)

Chemical References

• A 192621
• Benzoquinones
• Dioxoles
• Endothelin Receptor Antagonists
• Pyrazoles
• Pyrrolidines
• Receptor, Endothelin B
• Receptors, Endothelin
• SB 234551
• Arachidonic Acid
• phenylbenzoquinone

Topics

• Animals
• Arachidonic Acid (pharmacology)
• Benzoquinones (pharmacology, therapeutic use)
• Blotting, Southern
• Dermatitis (drug therapy, metabolism)
• Dioxoles (pharmacology, therapeutic use)
• Endothelin Receptor Antagonists
• Genotype
• Hyperalgesia (chemically induced, drug therapy)
• Mice
• Mice, Inbred BALB C
• Mice, Knockout
• Pain (drug therapy, metabolism)
• Polymerase Chain Reaction
• Pyrazoles (pharmacology, therapeutic use)
• Pyrrolidines (pharmacology, therapeutic use)
• Receptor, Endothelin B
• Receptors, Endothelin (genetics, metabolism)