Nakano T, Terawaki A, Arita H
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
J Pharmacobiodyn. 1987 Aug;10(8):408-20. doi: 10.1248/bpb1978.10.408.
The inhibitory mechanism of beta-lactam antibiotics on rat platelet activation was studied using carbenicillin (CBPC) as a representative of the antibiotics. CBPC suppressed all thrombin-induced cellular responses, including shape change, secretion and aggregation; however, it only suppressed aggregation of adenosine diphosphate (ADP)-induced responses. This suggested that ADP-binding to its own receptor was not affected by CBPC while thrombin-binding was inhibited. Inhibition of thrombin binding was confirmed using [125I]thrombin. In the case of ADP-stimulated platelets, fibrinogen-binding, which has an essential role for ADP-induced primary aggregation, was significantly suppressed by CBPC. Increase in a net negative charge of the membrane surface was observed after treatment of platelets with antibiotics and a good correlation was obtained between suppression of the platelet responses and increase in net negative charge of the antibiotics. These findings strongly suggest that the inhibition of ligand binding to their own receptors was due to the increase in the negative charge of the platelet membrane, which was probably caused by the antibiotic bound to the platelet membrane.
以羧苄青霉素（CBPC）作为β-内酰胺类抗生素的代表，研究了其对大鼠血小板活化的抑制机制。CBPC抑制了所有凝血酶诱导的细胞反应，包括形态变化、分泌和聚集；然而，它仅抑制了二磷酸腺苷（ADP）诱导反应的聚集。这表明ADP与其自身受体的结合不受CBPC影响，而凝血酶的结合受到抑制。使用[125I]凝血酶证实了凝血酶结合的抑制。在ADP刺激的血小板中，对ADP诱导的初级聚集起关键作用的纤维蛋白原结合被CBPC显著抑制。用抗生素处理血小板后，观察到膜表面净负电荷增加，并且在血小板反应的抑制与抗生素净负电荷增加之间获得了良好的相关性。这些发现强烈表明，配体与其自身受体结合的抑制是由于血小板膜负电荷的增加，这可能是由与血小板膜结合的抗生素引起的。
