TY - JOUR
T1 - Mesotrypsin, a brain trypsin, activates selectively proteinase-activated receptor-1, but not proteinase-activated receptor-2, in rat astrocytes
AU - Wang, Yingfei
AU - Luo, Weibo
AU - Wartmann, Thomas
AU - Halangk, Walter
AU - Sahin-Tóth, Miklós
AU - Reiser, Georg
PY - 2006/11
Y1 - 2006/11
N2 - Proteinase-activated receptors (PARs), a subfamily of G protein-coupled receptors, which are activated by serine proteases, such as trypsin, play pivotal roles in the CNS. Mesotrypsin (trypsin IV) has been identified as a brain-specific trypsin isoform. However, its potential physiological role concerning PAR activation in the brain is largely unknown. Here, we show for the first time that mesotrypsin, encoded by the PRSS3 (proteinase, serine) gene, evokes a transient and pronounced Ca2+ mobilization in both primary rat astrocytes and retinal ganglion RGC-5 cells, suggesting a physiological role of mesotrypsin in brain cells. Mesotrypsin mediates Ca2+ responses in rat astrocytes in a concentration-dependent manner, with a 50% effective concentration (EC50) value of 25 nm. The maximal effect of mesotrypsin on Ca2+ mobilization in rat astrocytes is much higher than that observed in 1321N1 human astrocytoma cells, indicating that the activity of mesotrypsin is species-specific. The pre-treatment of cells with thrombin or the PAR-1-specific peptide TRag (Ala-pFluoro-Phe-Arg-Cha-HomoArg- Tyr-NH2, synthetic thrombin receptor agonist peptide), but not the PAR-2-specific peptide, reduces significantly the mesotrypsin-induced Ca 2+ response. Treatment with the PAR-1 antagonist SCH79797 confirms that mesotrypsin selectively activates PAR-1 in rat astrocytes. Unlike mesotrypsin, the two other trypsin isoforms, cationic and anionic trypsin, activate multiple PARs in rat astrocytes. Therefore, our data suggest that brain-specific mesotrypsin, via the regulation of PAR-1, is likely to be involved in multiple physiological/pathological processes in the brain.
AB - Proteinase-activated receptors (PARs), a subfamily of G protein-coupled receptors, which are activated by serine proteases, such as trypsin, play pivotal roles in the CNS. Mesotrypsin (trypsin IV) has been identified as a brain-specific trypsin isoform. However, its potential physiological role concerning PAR activation in the brain is largely unknown. Here, we show for the first time that mesotrypsin, encoded by the PRSS3 (proteinase, serine) gene, evokes a transient and pronounced Ca2+ mobilization in both primary rat astrocytes and retinal ganglion RGC-5 cells, suggesting a physiological role of mesotrypsin in brain cells. Mesotrypsin mediates Ca2+ responses in rat astrocytes in a concentration-dependent manner, with a 50% effective concentration (EC50) value of 25 nm. The maximal effect of mesotrypsin on Ca2+ mobilization in rat astrocytes is much higher than that observed in 1321N1 human astrocytoma cells, indicating that the activity of mesotrypsin is species-specific. The pre-treatment of cells with thrombin or the PAR-1-specific peptide TRag (Ala-pFluoro-Phe-Arg-Cha-HomoArg- Tyr-NH2, synthetic thrombin receptor agonist peptide), but not the PAR-2-specific peptide, reduces significantly the mesotrypsin-induced Ca 2+ response. Treatment with the PAR-1 antagonist SCH79797 confirms that mesotrypsin selectively activates PAR-1 in rat astrocytes. Unlike mesotrypsin, the two other trypsin isoforms, cationic and anionic trypsin, activate multiple PARs in rat astrocytes. Therefore, our data suggest that brain-specific mesotrypsin, via the regulation of PAR-1, is likely to be involved in multiple physiological/pathological processes in the brain.
KW - Anionic trypsin
KW - Calcium signaling
KW - Cationic trypsin
KW - Mesotrypsin
KW - Proteinase-activated receptors
UR - http://www.scopus.com/inward/record.url?scp=33750077249&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33750077249&partnerID=8YFLogxK
U2 - 10.1111/j.1471-4159.2006.04105.x
DO - 10.1111/j.1471-4159.2006.04105.x
M3 - Article
C2 - 16903872
AN - SCOPUS:33750077249
SN - 0022-3042
VL - 99
SP - 759
EP - 769
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 3
ER -