Premium
Differential Ca 2+ responses induced by thrombin and thrombin‐receptor agonist peptides in HSY‐EA1 cells
Author(s) -
Tanimura Akihiko,
Shitara Akiko,
Nezu Akihiro,
Morita Takao,
Tojyo Yosuke
Publication year - 2003
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1016/j.cellbi.2003.10.001
Subject(s) - thrombin , thrombin receptor , agonist , cytosol , receptor , chemistry , peptide , protease activated receptor 2 , microbiology and biotechnology , protease activated receptor , endocrinology , medicine , biophysics , biochemistry , biology , enzyme linked receptor , enzyme , platelet
We examined the mechanism by which protease‐activated receptor (PAR)‐1 is desensitized by comparing the effect of thrombin and the soluble agonist peptide SFLLRN on Ca 2+ responses in HSY‐EA1 cells. Thrombin‐induced increases in cytosolic Ca 2+ concentrations ([Ca 2+ ] i ) returned to basal levels within 60 s, but SFLLRN generated a sustained [Ca 2+ ] i elevation. Interestingly, thrombin‐desensitized cells partially retained their ability to respond to SFLLRN. We desensitized PAR‐2 by pretreating cells with SLIGKV to confirm that this response was not due to PAR‐2, which can recognize SFLLRN. The highly specific PAR‐1 agonist peptide TFLLR also increased [Ca 2+ ] i in PAR‐2‐desensitized cells pretreated with thrombin. These observations indicate that thrombin disarms PAR‐1 from further proteolytic activation, but leaves the receptor responsive for non‐tethered ligands.