[Role of phosphatidylinositol 3-kinase and myosin light chain kinase during the activation of thrombin receptors].
The objective of study was to compare the influences of wortmannin on platelet aggregation and platelet membrane surface glycoproteins GPIb expression after thrombin receptor activation, and to investigate the role of phosphatidylinositol 3-kinase (PI3-K) and myosin light chain kinase (MLCK) in the course of thrombin receptor activation. Peptide SFLLRN (PAR1-AP) and AYPGKF (PAR4-AP) were used for stimulating platelet, and the changes of platelet aggregation and GPIb were analyzed with 100 nmol/L wortmannin (inhibitor of PI3-K) and 10 micromol/L wortmannin (inhibitor of MLCK). The results indicated that the platelet activation was influenced by either concentration of wortmannin in response to PAR stimulation. Platelet aggregation was apparently inhibited by 10 micromol/L wortmannin through both PAR peptides, and was slightly inhibited by 100 nmol/L wortmannin only under PAR1-AP activation. In addition, GPIbalpha internalization was partly inhibited by 100 nmol/L wortmannin in response to PAR1 (p < 0.05 at 1, 2, 5 min) and PAR4 (p < 0.05 at 2, 5, 10 min) activation. Meanwhile, 10 micromol/L wortmannin induced little change for GPIbalpha centralisation in the course of PAR activation, with a delayed restoration of surface GPIbalpha observed under PAR1-AP activation, and no change of GPIbalpha redistribution existed under PAR4-AP activation. It is concluded that the different roles of PI3-K and MLCK exist in the course of thrombin receptor activation. PI3-K accelerates the short course of GPIb centralisation for two PAR signal pathways, while MLCK inhibits the restoration of GPIbalpha in PAR1 pathway.
Han
Yue
Y
Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Jiangsu Institute of Hematology, The First Affiliated Hospital of Suzhou University, Suzhou, Jiangsu Province, China. hanyue06@yahoo.com
Gao
Hai-Li
HL
Zhang
Wei
W
Bai
Xia
X
Dai
Lan
L
Sheng
Wen-Hong
WH
Sun
Ai-Ning
AN
Wu
De-Pei
DP
Wang
Zhao-Yue
ZY
Ruan
Chang-Geng
CG
D000328:Adult; D000730:Androstadienes / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation; D018179:Receptors, Thrombin / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction; D000077191:Wortmannin
D000730:Androstadienes; D018179:Receptors, Thrombin; D058539:Phosphatidylinositol 3-Kinase; D009219:Myosin-Light-Chain Kinase; D000077191:Wortmannin