Is tissue-type plasminogen activator a neuromodulator?
Molecular and Cellular Neuroscience. 2004-04-01; 25(4): 594-601
DOI: 10.1016/j.mcn.2003.11.002
Lire sur PubMed
In the last few years, it has been evidenced that serine proteases play key roles
in the mammalian brain, both in physiological and pathological conditions. It has
been well established that among these serine proteases, the tissue-type
plasminogen activator (t-PA) is critically involved in development, plasticity,
and pathology of the nervous system. However, its mechanism of action remains to
be further investigated. By using pharmacological and immunological approaches,
we have evidenced in the present work that t-PA should be considered as a
neuromodulator. Indeed, we have observed that: (i). neuronal depolarization
induces a release of t-PA; (ii). this release of t-PA is sensitive to exocytosis
inhibition and calcium chelation; (iii). released t-PA modulates NMDA receptor
signaling and (iv). astrocytes are able to recapture extracellular t-PA through a
low-density lipoprotein (LDL) receptor-related protein (LRP)-dependent mechanism.