Dual effects of diclofenac on human platelet adhesion in vitro.
The effect of two non-steroidal anti-inflammatory drugs on the adhesion function of human platelets was evaluated. Platelets isolated from healthy human subjects were treated for 10 min with the indicated drugs and then incubated in fibrinogen-coated microwell plates in the absence or in the presence of ADP (10 microM) and thrombin (0.05 U/ml). After 1 h of incubation, adherent platelets were measured using an enzymatic assay. ADP- and thrombin-stimulated adhesion was significantly inhibited by high doses ( > 500 microM) of diclofenac, while doses ranging from 50 to 300 microM stimulated adhesion in the absence of agonists (resting platelets). A similar stimulatory effect on platelet adhesion was observed also with 200-500 microM flurbiprofen. Moreover, immunocytofluorimetry demonstrated that diclofenac dose-dependently (100-500 microM) induced the expression of GMP-140 and increased the expression of GPIIb/IIIa on the membrane of unstimulated platelets. High doses ( > 500 microM) of this drug inhibited thrombin-stimulated expression of GPIIb/IIIa and GMP-140.
Andrioli
G
G
Institute of Clinical Chemistry and Microscopy, University of Verona, Italy.
Lussignoli
S
S
Ortolani
R
R
Minuz
P
P
Vella
F
F
Bellavite
P
P
D000244:Adenosine Diphosphate / Q000494:pharmacology; D004008:Diclofenac / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005480:Flurbiprofen / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D019007:P-Selectin / Q000378:metabolism; D010973:Platelet Adhesiveness / Q000187:drug effects*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology; D015854:Up-Regulation
D019007:P-Selectin; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D004008:Diclofenac; D005480:Flurbiprofen; D000244:Adenosine Diphosphate; D013917:Thrombin