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Molecular Pharmacology

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Research ArticleArticle

Endothelin B Receptor Modulates Inflammatory Pain and Cutaneous Inflammation

Don E. Griswold, Stephen A. Douglas, Lenox D. Martin, T. Gregg Davis, Laura Davis, Zhaohui Ao, Mark A. Luttmann, Mark Pullen, Ponnal Nambi, Douglas W. P. Hay and Eliot H. Ohlstein
Molecular Pharmacology October 1999, 56 (4) 807-812;
Don E. Griswold
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Stephen A. Douglas
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Lenox D. Martin
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T. Gregg Davis
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Laura Davis
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Zhaohui Ao
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Mark A. Luttmann
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Mark Pullen
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Ponnal Nambi
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Douglas W. P. Hay
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Eliot H. Ohlstein
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Abstract

The role of endothelin B (ETB) receptors in inflammation and nociception was examined using ETB receptor knockout mice. Genotyping studies were used with tissues from ETB(+/+), ETB(+/−), and ETB(−/−) mice to confirm the loss of ETB 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 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 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 ETB receptor in mediation of inflammatory pain and cutaneous inflammatory responses in mice.

Footnotes

  • Send reprint requests to: Douglas W. P. Hay, Ph.D., Department of Pulmonary Pharmacology, SmithKline Beecham Pharmaceuticals, 709 Swedeland Rd, King of Prussia, PA 19406-0939. E-mail: douglas_w_hay{at}sbphrd.com

  • Abbreviations:
    ET
    endothelin
    ETA
    endothelin A receptor
    ETB
    endothelin B receptor
    IL
    interleukin-8
    PBQ
    phenylbenzoquinone
    AA
    arachidonic acid
    PCR
    polymerase chain reaction
    MPO
    myeloperoxidase
    • Received April 1, 1999.
    • Accepted July 16, 1999.
  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 56 (4)
Molecular Pharmacology
Vol. 56, Issue 4
1 Oct 1999
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Research ArticleArticle

Endothelin B Receptor Modulates Inflammatory Pain and Cutaneous Inflammation

Don E. Griswold, Stephen A. Douglas, Lenox D. Martin, T. Gregg Davis, Laura Davis, Zhaohui Ao, Mark A. Luttmann, Mark Pullen, Ponnal Nambi, Douglas W. P. Hay and Eliot H. Ohlstein
Molecular Pharmacology October 1, 1999, 56 (4) 807-812;

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Research ArticleArticle

Endothelin B Receptor Modulates Inflammatory Pain and Cutaneous Inflammation

Don E. Griswold, Stephen A. Douglas, Lenox D. Martin, T. Gregg Davis, Laura Davis, Zhaohui Ao, Mark A. Luttmann, Mark Pullen, Ponnal Nambi, Douglas W. P. Hay and Eliot H. Ohlstein
Molecular Pharmacology October 1, 1999, 56 (4) 807-812;
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