Differential Effects of β2-Adrenoceptor Desensitization on the IgE-Dependent Release of Chemical Mediators from Cultured Human Mast Cells

• Tsuji Toshikazu

  Department of Pharmacology, Gifu Pharmaceutical University

• Kato Toshinobu

  Department of Pharmacology, Gifu Pharmaceutical University

• Kimata Masahiro

  Department of Pharmacology, Gifu Pharmaceutical University

• Miura Toru

  Pharmaceutical Development Laboratory and Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd.

• Serizawa Isao

  Pharmaceutical Development Laboratory and Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd.

• Inagaki Naoki

  Department of Pharmacology, Gifu Pharmaceutical University

• Nagai Hiroichi

  Department of Pharmacology, Gifu Pharmaceutical University

書誌事項

タイトル別名

• Differential Effects of .BETA.2-Adrenoceptor Desensitization on the IgE-Dependent Release of Chemical Mediators from Cultured Human Mast Cells
• Differential Effects of ベータ 2 Adrenoceptor Desensitization on the IgE Dependent Release of Chemical Mediators from Cultured Human Mast Cells

抄録

In the present study, we examined the inhibitory effects of the β₂-adrenoceptor agonists isoproterenol, salbutamol, fenoterol, and clenbuterol, on the release of chemical mediators from cultured human mast cells after prolonged treatment with the agonists. Although preincubation of sensitized mast cells for 10 min with β₂-adrenoceptor agonists potently inhibited mediator release, prolongation of the preincubation period up to 240 min attenuated the inhibition. The attenuation of histamine release inhibition was potent when compared with that of prostaglandin D₂ (PGD₂) and cysteinyl leukotriene (LT) release inhibition. In contrast, forskolin inhibited mediator release and the inhibition increased gradually in proportion to the preincubation period. The reduced inhibition by the β₂-adrenoceptor agonists was compensated for by simultaneous treatment with cholera toxin. The β₂-adrenoceptor agonists elevated intracellular cAMP levels after 10-min incubation and the elevated levels were almost comparable to those after 240-min incubation. Forskolin elevated the intracellular cAMP levels more potently after incubation for 240 min than after 10 min. When mast cells were incubated for 3 d with the β₂-adrenoceptor agonists, similar attenuation of mediator release inhibition was observed. Elevation of intracellular cAMP levels was also attenuated, although β₂-adrenoceptor mRNA expression was potentiated. The present results collectively indicate that the attenuation of mediator release inhibition by β₂-adrenoceptor agonists under the present experimental conditions involves uncoupling between β₂-adrenoceptors and Gs proteins. Furthermore, the β₂-adrenoceptor desensitization causes differential attenuating effects on the inhibition of histamine, PGD₂, and LT release, suggesting that downstream events involved in each inhibitory pathway have different sensitivity to receptor desensitization.

収録刊行物

• Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ

  Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ 27 (10), 1549-1554, 2004

  公益社団法人 日本薬学会

キーワード

• β₂-adrenoceptor agonist
• desensitization
• human cultured mast cell
• IgE
• chemical mediator

詳細情報

• CRID: 1390001204624722816
• NII論文ID: 110003608652
• NII書誌ID: AA10885497
• DOI: 10.1248/bpb.27.1549
• ISSN: 13475215
• ISSN: 09186158
• NDL書誌ID: 7097202
• PubMed: 15467193
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I7097202
• Web Site: http://www.jstage.jst.go.jp/article/bpb/27/10/27_10_1549/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2006205028
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可