INHIBITORY EFFECT OF EGTA ON SEROTONIN TRANSPORT INTO RABBIT-BLOOD PLATELETS - POSSIBLE INVOLVEMENT OF THE GLYCOPROTEIN IIB IIIA COMPLEX/

We reported previously that serotonin (5-HT) transport was attenuated by treatment of platelets with EGTA, and that this inhibitory effect o f EGTA was restored by CaCl2. In the present study, the inhibitory eff ect of EGTA was found to be uncompetitive, and no inhibitory effect wa s observed when EGTA was added at 20 degrees C. Genistein and thyrphos tin A47, both protein tyrosine kinase inhibitors, inhibited Ca2+-induc ed restoration of 5-HT transport. In contrast, the protein tyrosine ph osphatase inhibitor phenylarsine oxide significantly augmented Ca2+-in duced restoration of 5-HT transport. These results might support the h ypothesis that the glycoprotein (GP) IIb/IIIa complex, a platelet memb rane integrin protein, might regulate 5-HT transport into blood platel ets. It is conceivable that Ca2+ chelation by EGTA might cause tempera ture-dependent dissociation of the GP IIb/IIIa complex, which results in the reduction of 5-HT transport. Rearrangement of the GP IIb/IIIa c omplex by replenishment of the Ca2+ binding sites might restore the EG TA-induced reduction of 5-HT transport.