Inhibitory action of gliclazide on platelet functions

Gliclazide (GC), an oral hypoglycemic agent, inhibits platelet functions, but its effective concentration is reported to be much higher in vitro than in vivo. To determine why, we compared its inhibitory effect measured by impedance aggregometry using citrated whole blood with that measured by turbidometry using platelet-rich plasma. In addition, to see how GC inhibits platelet functions, we examined its effects on arachidonic acid metabolism in platelets in an in vitro system. Impedance aggregometry was found to be more sensitive than turbidometry for detecting the inhibition of platelet aggregation, and revealed significant inhibition at 1 x 10(-4) M GC. GC reduced the amount of prostaglandin I2 (PGI2) needed to inhibit ADP-induced platelet aggregation and the adhesiveness of platelets to a rabbit vessel wall after their preincubation with 1 x 10(-3) M GC for 10 min. GC (1 x 10(-4) -1 x 10(-2) M) had no effect on platelet cyclo-oxygenase activity. GC inhibited thromboxane A2 (TXA2)-induced platelet aggregation, but had no effect on the aggregation triggered by addition of mixtures of arachidonic acid (AA) and inhibitors of key enzymes regulating various steps of AA metabolism in platelets. GC had no significant effect on PGI2-stimulated cyclic AMP (cAMP) production in platelets. These results show that the difference in the effective concentrations of GC reported to modulate platelet functions in vivo and in vitro is partly due to differences in the methods used to evaluate its effect: turbidometry evaluates platelet aggregability, but not other platelet functions modulated by GC in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)