INFLUENCE OF β-LACTAM ANTIBIOTICS ON THE PLATELETS IN VITRO EFFECTS OF SOME β-LACTAM ANTIBIOTICS ON THE BIOCHEMICAL RESPONSES OF RAT PLATELETS

The inhibitory mechanism of 3-lactam antibiotics on rat platelets were studied using carbenicil1 in (CBPC) as a representative of the antibiotics. CBPC suppressed all the thrombin-induced cellular responses including shape change, secretion, and aggregation, however, it only suppressed aggregation of ADP-induced responses. This suggests that ADP binding to its own receptor was not affected by the drug while that of thrombin was inhibited. Inhibition of thrombinbinding was confirmed using ¹²⁵CQSe 0f ADP-stimulated platelets, fibrinogen binding, which has an essential role for ADP-induced primary aggregation, was significantly suppressed by CBPC. Increase of a net negative charge of the membrane surface was observed after treatment of the platelets with antibiotics, and good correlation was obtained between suppression of the platelet responses and degree of net negativecharge of the antibiotics especially on the penicillin analogues. These findings strongly suggest that the inhibition of ligand binding to their own receptors is due to the increase of the negative charge of the platelet membranes which is probably caused by the antibiotic bound to the platelet membrane