Premium
Endothelins Stimulate Expression of Cyclooxygenase 2 in Rat Cultured Astrocytes
Author(s) -
Koyama Yutaka,
Mizobata Tsutomu,
Yamamoto Naoyoshi,
Hashimoto Hitoshi,
Matsuda Toshio,
Baba Akemichi
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0731004.x
Subject(s) - protein kinase c , astrocyte , prostaglandin e2 , cyclooxygenase , neuroglia , biology , phorbol , medicine , endocrinology , microbiology and biotechnology , tetradecanoylphorbol acetate , endothelin 1 , endothelins , signal transduction , biochemistry , enzyme , receptor , central nervous system
: Endothelin (ET) is one of the active endogenous substances regulating the functions of astrocytes. In the present study, we examined effects of ET on cyclooxygenase (COX) expression in cultured astrocytes. ET‐3 (100 n M ) caused transient increases in the expression of both COX2 mRNA and protein, but not those of COX1, in cultured astrocytes. ET‐induced COX2 mRNA expression was suppressed by 5 μg/ml actinomycin D, 30 μ M BAPTA/AM, inhibitors of protein kinase C (1‐100 n M staurosporin and 100 μ M H‐7), 2 μ M dexamethasone, and prolonged treatment with 100 n M phorbol 12‐myristate 13‐acetate. ET‐3 stimulated production of prostaglandin (PG) E 2 in cultured astrocytes. The effect of ET‐3 on the PGE 2 production was diminished by actinomycin D. Indomethacin and NS398, a selective COX2 inhibitor, comparably decreased both the basal and the ET‐stimulated PGE 2 production. Proliferation of cultured astrocytes was stimulated by 100 n M ET‐3, and the increased proliferation was reduced by co‐addition of 1 μ M PGE 2 . Treatment with 1 μ M PGE 2 caused astrocytic morphological changes accompanied by disappearance of stress fibers, a prominent structure of organized cytoskeletal actin in cultured astrocytes. In the presence of 10 n M ET‐3, PGE 2 did not show an effect on astrocytic actin organization. The present study shows that ET is an inducer of astrocytic COX2 and suggests that ET‐induced PGE 2 production through COX2 may be involved in the regulation of astrocytic functions.