The effect of several
gold complexes on the activity of
phospholipase C from human blood platelets was studied in vitro.
Aurothiomalate and auranofin--2 agents used for the chrysotherapy of
rheumatoid arthritis--,
gold chloride, (
triethylphosphine)gold chloride, and 5 newly synthesized (triethylphosphine)
gold complexes dose-dependently inhibited the
enzyme with IC50 values between 0.8 mumol/l ((
triethylphosphine)gold chloride) and over 100 mumol/l (
auranofin). None of the compounds affected
phospholipase A2 from human polymorphonuclear leukocytes at concentrations up to 100 mumol/l. Inhibition of
phospholipase C by (
triethylphosphine)gold chloride,
aurothiomalate, and compound 3 was not significantly different at substrate concentrations of 20 and 100 mumol/l
phosphatidylinositol, suggesting that these
gold complexes do not inhibit
phospholipase C by competing with the substrate. After confirming the Ca2+ dependence of the human platelet
phospholipase C by demonstrating inhibition by the Ca2+
chelators EDTA and
EGTA--but no inhibition by the Zn2+
chelator 1,10-phenanthroline--the inhibition of the
enzyme by (
triethylphosphine)gold chloride,
aurothiomalate, and compound 3 was studied at 3 different concentrations of Ca2+ in the range of 0.2 to 2 mmol/l. Inhibition by (
triethylphosphine)gold chloride was not affected by changes of Ca2+, whereas inhibition by
aurothiomalate and compound 3 was markedly suppressed by increasing the Ca2+ concentration.(ABSTRACT TRUNCATED AT 250 WORDS)