Site of action for the inhibition by gold sodium thiomalate of rabbit platelet activation.
The inhibitory action of the gold-based drug gold sodium thiomalate was investigated in rabbit platelets. Gold sodium thiomalate at concentrations of 0.25-13 x 10(-4) M inhibits collagen-, ADP-, and 9,11,dideoxy-11 alpha,9 alpha-epoxymethanoprostaglandin F2 alpha (U46619)-induced aggregation as well as collagen- and U46619-induced serotonin release. This inhibition occurs in both Tyrodes-albumin or Tyrodes-gelatin buffer systems. Preincubation of gold sodium thiomalate with platelets resulted in less inhibition as the time of preincubation increased. The inhibitory effect of gold sodium thiomalate could be removed by washing the platelets. Other sulfhydryl-reacting compounds, such as D-penicillamine, thiomalic acid, 5,5'-dithiobis-2-nitrobenzoic acid, and 6,6'-dithiodinicotinic acid, were all capable of inhibiting collagen-induced aggregation and serotonin release. Evidence is presented that gold sodium thiomalate interferes with the activation of rabbit platelets by several activators, that this action of gold sodium thiomalate is similar to the action of other sulfhydryl-reacting agents, that this inhibition is likely occurring at the membrane, and that the action of the drug is not dependent on the presence of albumin.
McKague
K M
KM
Department of Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
Lock
C J
CJ
McCrae
F
F
Smith
W E
WE
Buchanan
H
H
Kean
W F
WF
Reglinski
J
J
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects; D006052:Gold Sodium Thiomalate / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D012701:Serotonin / Q000097:blood; D012709:Serum Albumin / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000494:pharmacology
D010975:Platelet Aggregation Inhibitors; D012709:Serum Albumin; D013438:Sulfhydryl Compounds; D006052:Gold Sodium Thiomalate; D012701:Serotonin