title: Roles of dopamine receptor subtypes in mediating modulation of T lymphocyte function.
abstract: OBJECTIVE
  Dopamine exists in the immune system and has obvious immunomodulating action. However, receptor mechanism underlying the dopamine immunomodulation remains to be clarified. In the present study, we provide the evidence for existence of dopamine receptor subtypes in T lymphocytes and show the roles of the receptors and the receptor-coupled signaling in mediating the dopamine immunomodulation.
  
  
  METHODS
  The purified T lymphocytes from the mesenteric lymph nodes of mice were detected for expressions of all five subtypes of dopamine receptor mRNAs by reverse transcription-polymerase chain reaction. Lymphocyte proliferation and production of interferon-γ (IFN-γ) and interleukin-4 (IL-4) in response to concanavalin A (Con A) were measured by colorimetric methyl-thiazole-tetrazolium assay and cytometric bead array, respectively, after the cells were exposed to dopamine D1-like or D2-like receptor agonists and antagonists. Meanwhile, content of cAMP and phosphorylation of cAMP-response element-binding (CREB) in the lymphocytes were examined by 125I-cAMP radioimmunoassay and Western blot assay, respectively.
  
  
  RESULTS
  T lymphocytes expressed all the five subtypes of dopamine receptor mRNAs, i.e., D1, D2, D3, D4 and D5 receptors. SKF38393, an agonist of dopamine D1-like receptors (D1 and D5 receptors) only reduced the IFN-γ production, but did not significantly affect the proliferative response, IL-4 production, cAMP content or CREB activation of the lymphocytes. The SKF38393-induced decrease in IFN-γ level was blocked by the D1-like receptor antagonist SCH23390. Quinpirole, an agonist of dopamine D2-like receptors (D2, D3 and D4 receptors) attenuated the lymphocyte proliferation to Con A, and decreased the IFN-γ but increased the IL-4 production. Meanwhile, the quinpirole diminished the cAMP content and the phosphorylated CREB level in the lymphocytes. All the quinpirole-induced changes were reversed by dopamine D2-like receptor antagonist haloperidol.
  
  
  CONCLUSIONS
  Five dopamine receptor subtypes of the two families, D1-like and D2-like receptors, exist on T lymphocytes of mice. Of the two families, D2-like receptors are more important in mediating modulation of T cell function than D1-like receptors. D2-like receptors are involved in suppression of T helper 1 (Th1) cell function and enhancement of Th2 cell function through negative link to cAMP-CREB pathway.
authors.affiliation: Department of Physiology, Nantong University, Nantong, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.forename: Ao-Wang
authors.initials: AW
authors.lastname: Qiu
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Peng
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Hui-Wei
authors.initials: HW
authors.lastname: Huang
authors.forename: Yi-Hua
authors.initials: YH
authors.lastname: Qiu
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D015153:Blotting, Western; D050882:CREB-Binding Protein / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D007371:Interferon-gamma / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D011954:Receptors, Dopamine / Q000145:classification / Q000235:genetics / Q000276:immunology; D017447:Receptors, Dopamine D1 / Q000276:immunology*; D017448:Receptors, Dopamine D2 / Q000276:immunology*; D050637:Receptors, Dopamine D3 / Q000276:immunology; D050638:Receptors, Dopamine D4 / Q000276:immunology; D050641:Receptors, Dopamine D5 / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
chemical_list: D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D012333:RNA, Messenger; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C534628:SCH 23390; D050638:Receptors, Dopamine D4; D050641:Receptors, Dopamine D5; D015847:Interleukin-4; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D007371:Interferon-gamma; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse