Abstract
Neurite retraction and reversal of astrocyte stellation triggered by the serine protease
thrombin are receptor-mediated events. This article summarizes the current knowledge
about the cellular effects that are induced by thrombin and its receptor in neural
cells. The data presented show that the thrombin receptor messenger RNA is expressed
in cultured astrocytes and that the reversal of stellation caused by thrombin in these
cells is prevented by the protein kinase inhibitor staurosporine. Peptides based in
sequence on the tethered ligand domain of the thrombin receptor were shown to mimic
the effect of thrombin in most systems investigated. Platelets of some species, however,
aggregate only in response to thrombin but not to the peptides. This observation is
confirmed here. Rodent receptor-activating peptides did not cause aggregation of rat
or mouse platelets. In contrast, all peptides triggered reversal of stellation in
rat astrocytes and neurite retraction in mouse neuroblastoma cells, supporting the
proposed mechanism of cleavage-induced receptor activation in neural cells. Finally,
evidence is presented that serum withdrawal causes a decrease in the amount of the
thrombin receptor mRNA in different types of neuronal cells. The possible role played
by the thrombin receptor in the nervous system is discussed.
Keywords:
Astrocytes - cAMP - lysophosphatidic acid - neurite retraction - platelets
