title: Therapeutic effect of D1-like dopamine receptor antagonist on collagen-induced arthritis of mice.
abstract: Dopamine activates D1-like and D2-like receptors (D1R and D2R). While D1R antagonists have ameliorated the severity of disease in some experimental autoimmune models of mice by promoting interferon (IFN)-γ and inhibiting interleukin (IL)-17 production by T cells, dopamine effects in the immune system are reportedly diverse. To investigate the impact of D1R blockade on an animal model of rheumatoid arthritis (RA), DBA/1 mice with collagen-induced arthritis (CIA) were treated with a selective D1R antagonist, SCH23390, after the primary immunization. This treatment suppressed the severity of the CIA. Nevertheless, serum levels of antibodies to type II collagen were not affected by the treatment. Th1/Th17 differentiation of splenic T cells in the treated animals was not biased. In vitro, when bone marrow-derived macrophages were stimulated in the presence of the D1R antagonist SCH23390, alteration of inflammatory cytokine expression was not observed, but their in vitro differentiation to osteoclasts was inhibited. Co-administration of a selective D1R agonist, A68930, abrogated the in vivo anti-arthritic effect and the in vitro suppression of osteoclastogenesis by the D1R antagonist. Our results argue that D1R blockade is potentially a new approach to the treatment of RA. Its effect could be partly attributable to the inhibition of osteoclastogenesis.
authors.affiliation: Global Center of Excellence (GCOE) Program, Department of Medicine and Rheumatology, Graduate School of Medical and Dental Sciences, International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Nakashioya
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Nakano
authors.forename: Naoko
authors.initials: N
authors.lastname: Watanabe
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Miyasaka
authors.forename: Sho
authors.initials: S
authors.lastname: Matsushita
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kohsaka
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000276:immunology; D001552:Benzazepines / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects; D011859:Radiography; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors*
chemical_list: D001552:Benzazepines; D002839:Chromans; D016207:Cytokines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; C534628:SCH 23390; C065380:A 68930