Carbenicillin and Penicillin G Inhibit Platelet Function In Vitro by Impairing the Interaction of Agonists with the Platelet Surface

Sanford J. Shattil; Joel S. Bennett; Margaret McDonough; Judy Turnbull

doi:10.1172/JCI109676

Carbenicillin and Penicillin G Inhibit Platelet Function In Vitro by Impairing the Interaction of Agonists with the Platelet Surface

Sanford J. Shattil, Joel S. Bennett, Margaret McDonough, and Judy Turnbull

Published February 1, 1980 - More info

View PDF

Abstract

Carbenicillin or penicillin G administered in large doses can cause a bleeding diathesis as a result of platelet dysfunction. These antibiotics also inhibit platelet aggregation in vitro, although several-fold larger concentrations of drug are required to demonstrate this effect. We wondered whether these antibiotics might impair platelet function by interfering with the initial step of platelet activation: the binding of agonists to their specific receptors on the platelet surface.

Platelet aggregation and [¹⁴C]serotonin release induced by epinephrine were competitively inhibited by carbenicillin and penicillin G in vitro. At antibiotic concentrations that inhibited platelet function by more than 80%, the affinity of platelet α-adrenergic receptors for the α-adrenergic antagonist, [³H]dihydroergocryptine, and for epinephrine was reduced twofold by carbenicillin and sixfold by penicillin G (P < 0.01). Platelet aggregation and [¹⁴C]serotonin release stimulated by ADP were also competitively inhibited by these antibiotics. In addition, carbenicillin reduced the incorporation of an ADP affinity label, 5′-p-fluorosulfonylbenzoyl [³H]adenosine, into its binding protein in platelet membranes. Moreover, both carbenicillin and penicillin G impaired the interaction of von Willebrand factor with platelets as evidenced by their inhibition of the agglutination of formalin-fixed platelets by ristocetin, snake venom, or bovine factor VIII.

These studies demonstrate that carbenicillin and penicillin G inhibit platelet function in vitro by impairing the interaction of several agonists with their specific receptors on the platelet surface membrane. If this were mechanism operative in vivo, it could account for the hemorrhagic as well as the potential antithrombotic effects of these antibiotics.