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Reciprocal Modulation of Astrocyte Stellation by Thrombin and Protease Nexin‐1
Author(s) -
Cavanaugh Kathleen P.,
Gurwitz David,
Cunningham Dennis D.,
Bradshaw Ralph A.
Publication year - 1990
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 - 10.1111/j.1471-4159.1990.tb01228.x
Subject(s) - astrocyte , modulation (music) , thrombin , neuroscience , chemistry , microbiology and biotechnology , protease , biophysics , biology , biochemistry , physics , enzyme , immunology , central nervous system , platelet , acoustics
When cultured astroglia are treated with agents that elevate intracellular cyclic AMP, they become process‐bearing stellate cells and resemble differentiated astrocytes in vivo. Thrombin rapidly reversed the stellation induced by dibutyryl cyclic AMP, forskolin, or isoproterenol in cultured rat astrocytes; half‐maximal and maximal effects occurred at 0.5 and 8 p M , respectively. The proteolytic activity of thrombin was required for stellation reversal, as thrombin derivatized at its catalytic site serine with a diisopropylphospho group was inactive. Two thrombin inhibitors, protease nexin‐1 and hirudin, blocked and reversed the effect of thrombin. The stellation reversal effect of thrombin was specific, as 300–1,000‐fold higher concentrations of other serine proteinases, including plasmin, urokinase, trypsin, and T cell serine proteinase‐1, were ineffective. Thrombin is a mitogen for astrocytes at concentrations in excess of 30 p M. Thrombin increased both cell number and ornithine decarboxylase activity, an early marker for mitogenic stimulation, in astrocyte cultures. The lowest thrombin concentrations that completely reversed astrocyte stellation, however, did not increase ornithine decarboxylase activity. Moreover, several other mitogens for astrocytes did not reverse dibutyryl cyclic AMP‐induced stellation. Thus, the stellation reversal effect of thrombin is distinct from the mitogenic response.