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Role of Gαq and phospholipase C‐β2 in human platelets activation by thrombin receptors PAR1 and PAR4: studies in human platelets deficient in Gαq and phospholipase C‐β2
Author(s) -
Vaidyula Vijender R.,
Rao A. Koneti
Publication year - 2003
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2003.04296.x
Subject(s) - platelet , thrombin , phospholipase c , protease activated receptor , platelet activation , medicine , receptor , endocrinology , thrombin receptor , phospholipase , biology , chemistry , microbiology and biotechnology , biochemistry , enzyme
Summary. Thrombin responses in human platelets are mediated by the protease‐activated receptors (PAR), PAR1 and PAR4. The signalling pathways mediating PAR activation have not been fully delineated for human platelets. We assessed cytoplasmic Ca 2+ mobilization in response to activation with thrombin and PAR1 (SFLLRN) and PAR4 (GYPGKF) peptides in two patients whose platelets were deficient in two major signalling proteins, Gαq or phospholipase (PLC)‐β2. In normal platelets, thrombin induced a biphasic Ca 2+ response with a rapid rise to a peak followed by a sustained elevation in Ca 2+ . The peak Ca 2+ rise was impaired in both patients at lower thrombin concentrations. At higher concentrations, it was decreased in PLC‐β2‐deficient platelets; the sustained Ca 2+ elevation observed in normal and Gαq‐deficient platelets was reduced in PLC‐β2‐deficient platelets. The response to SFLLRN was decreased in both patients at lower concentrations. The peak Ca 2+ in response to GYPGKF was reduced in both patients; the sustained Ca 2+ increase was markedly decreased in PLC‐β2‐deficient platelets. These studies provide evidence that, in human platelets, both Gαq and PLC‐β2 play a major role in responses to PAR1 and PAR4 activation, and that PLC‐β2 is required for the sustained Ca 2+ rise upon thrombin activation.