title: Molecular mechanisms for alpha2-adrenoceptor-mediated regulation of synoviocyte populations.
abstract: The sympathetic nervous system has been indicated to influence the severity of inflammatory disease including rheumatoid arthritis. In this study, we elucidated the effects of catecholamine on the synovial cell populations. Stimulation with epinephrine or norepinephrine for 1-2 weeks dose- and time-dependently increased the number of synovial A (macrophage-like) cells but decreased that of B (fibroblast-like) cells. These responses in A and B cells were inhibited by the alpha2-antagonist yohimbine, the G-protein inactivator pertussis toxin and the phospholipase C (PLC) inhibitor U-73122. Furthermore, the protein kinase C (PKC) inhibitor calphostin C and mitogen-activated protein (MAP) kinase inhibitors PD98059 and wortmannin also abolished the norepinephrine effects on A and B cell numbers. In A cells cloned from an A and B cell mixture, norepinephrine also increased the cell number. In immunoblotting and immunocytostaining analyses, among the PKC isozymes, only PKC betaII immunoreactivity was observed in the cytoplasm of unstimulated A and B cells. After alpha2-adrenoceptor stimulation, PKC betaII immunoreactivity increased in the plasma membranes of both A and B cells with decreases in the cytoplasm. These findings indicated that alpha2-adrenoceptor stimulation of type A and B synoviocytes produced an increase and a decrease in the respective cell number, probably through Gi-coupled PLC activation and the resulting stimulation of the PKC betaII/MAP kinase.
authors.affiliation: Department of Pharmacology, Kansai Medical University, Moriguchi City, Osaka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Mishima
authors.forename: H
authors.initials: H
authors.lastname: Otani
authors.forename: T
authors.initials: T
authors.lastname: Tanabe
authors.forename: H
authors.initials: H
authors.lastname: Kawasaki
authors.forename: A
authors.initials: A
authors.lastname: Oshiro
authors.forename: N
authors.initials: N
authors.lastname: Saito
authors.forename: R
authors.initials: R
authors.lastname: Ogawa
authors.forename: C
authors.initials: C
authors.lastname: Inagaki
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002452:Cell Count; D002478:Cells, Cultured; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D009638:Norepinephrine / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D064546:Protein Kinase C beta; D011817:Rabbits; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000502:physiology*; D013583:Synovial Membrane / Q000166:cytology*
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D018341:Receptors, Adrenergic, alpha-2; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D020928:Mitogen-Activated Protein Kinases; D019204:GTP-Binding Proteins; D009638:Norepinephrine; D004837:Epinephrine