Effect of PCR 4099 on ADP-induced calcium movements and phosphatidic acid production in rat platelets.
Antiplatelet activity of PCR 4099, an analogue of ticlopidine, resides in its specific effect against exogenous as well as released ADP. This study investigated in rat platelets the effects of the drug on ADP-induced shape change, elevation of cytosolic free Ca2+ concentration ([Ca2+]i) and hydrolysis of inositol phospholipids, monitored as [32P]phosphatidic acid formation. Shape change and influx of Ca2+ ions across the plasma membrane were not modified after PCR 4099 administration using aspirin-treated platelets. On the other hand, phosphatidic acid formation and calcium mobilization from internal stores were strongly inhibited. These results suggest that PCR 4099 leaves intact the machinery involved in ADP-induced platelet shape change and influx of calcium ions, but inhibits an early step in the ADP-response coupling leading to inositol phospholipid hydrolysis and aggregation.
Feliste
R
R
INSERUM Unité 101, Hôpital Purpan, Toulouse, France.
Simon
M F
MF
Chap
H
H
Douste-Blazy
L
L
Defreyn
G
G
Maffrand
J P
JP
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000097:blood*; D000077144:Clopidogrel; D005340:Fibrinogen / Q000378:metabolism; D066298:In Vitro Techniques; D010712:Phosphatidic Acids / Q000097:blood*; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010738:Type C Phospholipases / Q000097:blood
D010712:Phosphatidic Acids; D000244:Adenosine Diphosphate; D005340:Fibrinogen; D000077144:Clopidogrel; D010738:Type C Phospholipases; D013988:Ticlopidine; D002118:Calcium