Jpn. J. Pharmacol. 85 (3), 214-226 (2001)

Molecular Mechanisms for a2-Adrenoceptor-Mediated Regulation of Synoviocyte Populations

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

1Department of Pharmacology, and 2Department of Orthopaedic Surgery, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi City, Osaka 570-8506, Japan
3Laboratory of Molecular Pharmacology, Biosignal Research Center, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan
*Corresponding author. FAX: +81-6-6992-2940

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 a2-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 bII immunoreactivity was observed in the cytoplasm of unstimulated A and B cells. After a2-adrenoceptor stimulation, PKC bII immunoreactivity increased in the plasma membranes of both A and B cells with decreases in the cytoplasm. These findings indicated that a2-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 bII/MAP kinase.

Keywords: Synoviocyte, a2-Adrenoceptor stimulation, Cell population, Protein kinase C bII

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