title: D1-like dopamine receptors antagonist inhibits cutaneous immune reactions mediated by Th2 and mast cells.
abstract: BACKGROUND
  Dopamine transduces signals via five subtypes of G protein-coupled receptors. Among these subtypes, the D1 and D5 receptors belong to the D1-like group. Although dopamine is known to mediate immune responses, its involvement in cutaneous immunity remains unclear.
  
  
  OBJECTIVE
  The aim of this study is to determine the role of dopamine and its D1-like receptors in cutaneous immune responses.
  
  
  METHODS
  By using the D1-like receptor antagonist SCH 23390, we examined the role of D1-like receptors in murine models of Th1-type contact hypersensitivity and Th2-type atopic dermatitis in vivo, and in mast cells and Th2 cell differentiation in vitro.
  
  
  RESULTS
  Administration of SCH 23390 did not affect Th1-type contact hypersensitivity but suppressed the immediate-type reaction (ITR) and the late phase reaction (LPR) in the atopic dermatitis model. In addition, SCH 23390-treated mice showed higher IFN-γ and lower IL-4 mRNA levels in the ear skin of challenged mice than did non-treated mice as analyzed by real-time RT PCR. Consistently, the passive cutaneous anaphylaxis reaction was significantly reduced in SCH 23390-treated mice. Moreover, dopamine enhanced mast cell degranulation and Th2 cell differentiation, and both activities were abrogated by SCH 23390.
  
  
  CONCLUSIONS
  These findings suggest that the D1-like receptors mediate immediate and late phase skin reactions by promoting Th2 induction and mast cell degranulation.
authors: Department of Dermatology, University of Occupational and Environmental Health, Kitakyusyu, Japan. tomoko-n@med.uoeh-u.ac.jp
authors: Tomoko
authors: T
authors: Mori
authors: Kenji
authors: K
authors: Kabashima
authors: Shoko
authors: S
authors: Fukamachi
authors: Etsushi
authors: E
authors: Kuroda
authors: Jun-ichi
authors: J
authors: Sakabe
authors: Miwa
authors: M
authors: Kobayashi
authors: Saeko
authors: S
authors: Nakajima
authors: Kazuhisa
authors: K
authors: Nakano
authors: Yoshiya
authors: Y
authors: Tanaka
authors: Sho
authors: S
authors: Matsushita
authors: Motonobu
authors: M
authors: Nakamura
authors: Yoshiki
authors: Y
authors: Tokura
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D015550:Cell Degranulation / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003876:Dermatitis, Atopic / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D003877:Dermatitis, Contact / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D004195:Disease Models, Animal; D018492:Dopamine Antagonists / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D050641:Receptors, Dopamine D5 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D013997:Time Factors
chemical_list: D001552:Benzazepines; D018492:Dopamine Antagonists; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; C534628:SCH 23390; D050641:Receptors, Dopamine D5; D015847:Interleukin-4; D007371:Interferon-gamma