The Thrombin Receptor in the Nervous System

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.