Abstract:
:U73122 ((1-[6-(( 17beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)exyl]-1H-p yrrole-2,5-dione)) is generally used as a selective inhibitor of phospholipase C (PLC) and the related rise in cytosolic Ca2+. Recently, by using hepatocytes, it was suggested that its action sites are different for PLC activation and increase in Ca2+ concentration. To verify whether U73122 has different sites for inhibiting PLC activation and calcium responses in human platelets, aggregation, Mn2+ influx, cytosolic Ca2+ increase and PLC activation were studied in response to thrombin and the synthetic agonist of the thromboxane receptor U46619 (9,11-dideoxy-9alpha,11alpha-methanoepoxyprostaglandin F2alpha). With both agonists, U73122 inhibited aggregation, Mn2+ influx and the enhancement of cytosolic calcium at concentrations of 2 microM or lower, while 10 microM was necessary to inhibit PLC activation. Our results suggested that U73122 is much more active in antagonizing Ca2+ channels, both the intracellular ones, which are activated by formation of inositol 1,4,5 P3 and those present on plasma membrane, than in reducing the activation of PLC.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Pulcinelli FM,Gresele P,Bonuglia M,Gazzaniga PPdoi
10.1016/s0006-2952(98)00146-4subject
Has Abstractpub_date
1998-12-01 00:00:00pages
1481-4issue
11eissn
0006-2952issn
1873-2968pii
S0006-2952(98)00146-4journal_volume
56pub_type
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