Thrombin receptor peptides induce shape change in neonatal murine astrocytes in culture

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Abstract
Astrocytes appear star‐shaped in the brain, increasingly so after injury. When astroglia are cultures in serum‐containing medium, they exhibit a flat, fibroblast‐like morphology. In serum‐free medium, astrocytes become stellate, with many long processes. The serine protease α‐thrombin mimics the effects of serum at subnanomolar concentractions, whereas the thrombin‐inhibiting serpin, protease nexin I (PNI), reverses the thrombin effect. In our current experiements, murine neonatal spinal cord astrocytes became stellate after 4 hr in serum‐free medium, while cortical astrocytes requires 12 hr in serum‐free medium for stellation. Astrocytes from either region flattened after 60 min in medium containing 3.0 to 300 pM proteoloytically active human α‐thrombin. After 12 hr in thrombin‐containing medium, 98% of the astrocytes had a flattened morphology. No flattening occured if α‐thrombin was replaced by γ‐thrombin, which has its fibrinogen‐recognition exosite disrupted. PNI added at 1 nM to serum‐containing medium caused stellation after 3 hr, and astroglia were 50% stellate by 12 hr. The effect of thrombin was mimicked by a 7‐amino acid peptide (TRP‐7) action on astrocytes. These results indicate that astrocytes possess a cell surface receptor for thrombin, similar to that described for platelets, endothelial cells, and neurons. © 1994 Wiley‐Liss, Inc. This article is a US Government work and, as such, is in the public domain in the United States of America.