Molecular Mechanisms for α2-Adrenoceptor-Mediated Regulation of Synoviocyte Populations

The Japanese Journal of Pharmacology

Ryokei Ogawa²  Akihiro Oshiro¹  Katsuyuki Mishima¹  Hiroshi Kawasaki¹  Naoaki Saito³  Takatoshi Tanabe²  Chiyoko Inagaki¹  Hitomi Otani¹ 

[1] Department of Pharmacology;Department of Orthopaedic Surgery, Kansai Medical University;Laboratory of Molecular Pharmacology, Biosignal Research Center, Kobe University

关键词: Synoviocyte;    α2-Adrenoceptor stimulation;    Cell population;    Protein kinase C βII;   

DOI  :  10.1254/jjp.85.214

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(41)Cited-By(10)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 α2-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 βII immunoreactivity was observed in the cytoplasm of unstimulated A and B cells. After α2-adrenoceptor stimulation, PKC βII immunoreactivity increased in the plasma membranes of both A and B cells with decreases in the cytoplasm. These findings indicated that α2-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 βII/MAP kinase.

【 授权许可】

Unknown