| Sheu JR, Hsiao G, Luk HN, Chen YW, Chen TL, Lee LW, Lin CH, Chou DS |
------>authors3_c=None ------>paper_class1=1 ------>Impact_Factor=None ------>paper_class3=2 ------>paper_class2=1 ------>vol=96 ------>confirm_bywho=tlc ------>insert_bywho=TLC ------>Jurnal_Rank=None ------>authors4_c=None ------>comm_author= ------>patent_EDate=None ------>authors5_c=None ------>publish_day=None ------>paper_class2Letter=None ------>page2=658 ------>medlineContent= ------>unit=E0121 ------>insert_date=20020325 ------>iam=5 ------>update_date= ------>author=??? ------>change_event=5 ------>ISSN=None ------>authors_c=None ------>score=500 ------>journal_name=Anesthesiology ------>paper_name=Mechanisms involved in the antiplatelet activity of midazolam in human platelets. ------>confirm_date=20020328 ------>tch_id=087025 ------>pmid=11873041 ------>page1=651 ------>fullAbstract=BACKGROUND: Midazolam is widely used as a sedative and anesthetic induction agent. The aim of this study was to systematically examine the inhibitory mechanisms of midazolam in platelet aggregation. METHODS: The inhibitory mechanisms of midazolam in platelet aggregation were explored by means of analysis of the platelet glycoprotein IIb-IIIa complex, phosphoinositide breakdown, intracellular Ca+2 mobilization, measurement of membrane fluidity, thromboxane B2 formation, and protein kinase C activity. RESULTS: In this study, midazolam dose-dependently (6-26 microm) inhibited platelet aggregation in human platelets stimulated by agonists. Midazolam also dose-dependently inhibited phosphoinositide breakdown and intracellular Ca+2 mobilization in human platelets stimulated by collagen. Midazolam (6-26 mum) significantly inhibited thromboxane A2 formation stimulated by collagen in human platelets. Moreover, midazolam (15 and 26 mum) dose-dependently decreased the fluorescence of platelet membranes tagged with diphenylhexatriene. Rapid phosphorylation of a platelet protein of Mr 47,000 (P47), a marker of protein kinase C activation, was triggered by collagen (2 microg/ml). This phosphorylation was markedly inhibited by midazolam (26 microm). CONCLUSIONS: These results indicate that the antiplatelet activity of midazolam may be involved in the following pathways: the effects of midazolam may initially be caused by induction of conformational changes in platelet membrane, leading to a change in the activity of phospholipase C, and subsequent inhibition of phosphoinositide breakdown and thromboxane A2 formation, thereby leading to inhibition of both intracellular Ca+2 mobilization and phosphorylation of P47 protein. ------>tmu_sno=None ------>sno=5016 ------>authors2=None ------>authors3=None ------>authors4=None ------>authors5=None ------>authors6=None ------>authors6_c=None ------>authors=Sheu JR, Hsiao G, Luk HN, Chen YW, Chen TL, Lee LW, Lin CH, Chou DS ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c=None ------>publish_area=None ------>updateTitle=Mechanisms involved in the antiplatelet activity of midazolam in human platelets. ------>language=2 ------>check_flag= ------>submit_date= ------>country=None ------>no= ------>patent_SDate=None ------>update_bywho= ------>publish_year=2002 ------>submit_flag= ------>publish_month=None |