Characterization of proteinase-activated receptor 2 signalling and expression in rat hippocampal neurons and astrocytes

Bushell, T. and Plevin, R.J. and Cobb, S. and Irving, A.J. (2006) Characterization of proteinase-activated receptor 2 signalling and expression in rat hippocampal neurons and astrocytes. Neuropharmacology, 50 (6). pp. 714-725. ISSN 0028-3908

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Abstract

Proteinase-activated receptors (PARs1–4) have recently been identified as the molecular entity underlying the cellular effects of serine proteinases. In the present study we have investigated PAR2 signalling, expression and desensitization using cultured and acute slice preparations. Trypsin, SLIGRL and 2f-LIGKV-OH, agonists for PAR2, induced a transient increase in intracellular Ca2+ levels in both neurons and astrocytes, via activation of the phospholipase C/IP3 pathway. Furthermore, a single application of trypsin, but not SLIGRL nor 2f-LIGKV-OH, leads to prolonged desensitization of PAR2 responses. PAR2 immunoreactivity was observed in neurons (glutamatergic and GABAergic) and astrocytes within cultures and acute slices, with prominent labelling in neuronal somata and proximal dendrites. Functionally, cultured neurons which exhibited the highest levels of PAR2 labelling, also exhibited the largest Ca2+ signals upon PAR2 activation. Given the importance of Ca2+ signalling in hippocampal synaptic plasticity and neurodegeneration, PAR2 may play a key modulatory role in these processes.