The Effect of Local Anaesthetics and Antiarrhythmic Agents on the Responses of Rabbit Platelets to ADP and Thrombin

Summary

Local anaesthetics and antiarrhythmic agents produced changes in responses of rabbit platelets to ADP and thrombin that varied with the agent and its concentration. In high concentrations all local anaesthetics decreased aggregation rates. At lower concentrations several local anaesthetics increased aggregation rates. Depending on the agonist and local anaesthetic, increases were produced at all or only at low or high agonist concentrations. Local anaesthetics failed to influence shape change except at concentrations much greater than those which inhibited aggregation. Inhibition of aggregation by procaine was potentiated by small organic anions suggesting effects at different sites on the platelet membrane. The inhibitory effect of local anaesthetics was decreased by increasing Ca. Kinetic analysis indicated different mechanisms for this Ca effect, i. e., predominantly competitive for procaine or lidocaine and predominantly non-competitive for tetracaine or ethyl lidocaine. Local anaesthetics may affect aggregation by modifying the participation of Ca in this process.

Keywords

Platelets - Aggregation - Local anaesthetics - Antiarrhythmic agents

• References

• 1 O’Brien JR. The adhesiveness of native platelets and its prevention. J Clin Pathol 1961; 14: 140-149
• 2 O’Brien JR. Platelet aggregation. Part I. Some effects of the adenosine phosphates, thrombin, and cocaine upon platelet adhesiveness. J Clin Pathol 1962; 15: 446-455
• 3 Aledort LM, Niemetz J. Dissociation of platelet aggregation from clot retraction, potassium loss, and adenosine triphosphatase activity. Proc Soc exp Biol Med 1968; 128: 658-661
• 4 Feinstein MB, Fiekers J, Fraser C. An analysis of the mechanism of local anaesthetic inhibition of platelet aggregation and secretion. J Pharmacol Exp Ther 1976; 197: 215-228
• 5 Anderson ER, Foulks JG. The effect of small organic anions on aggregation and shape change of rabbit platelets. Thromb Haemostas 1978; 40: 43-60
• 6 Foulks JG, Perry FA. Increased sensitivity of frog skeletal muscle to procaine in the presence of organic anions. Can J Physiol Pharmacol 1978; 56: 739-746
• 7 Bom GV R, Cross MJ. The aggregation of blood platelets. J Physiol 1963; 168: 178-195
• 8 Baumgartner HR, Bom GV R. Effects of 5-hydroxytryptamine on platelet aggregation. Nature 1968; 218: 137-141
• 9 Baumgartner HR, Bom GV R. The relation between the 5-hydroxytryptamine content and aggregation of rabbit platelets. J Physiol 1969; 201: 397-408
• 10 Bondani A, Karler R. Interaction of Ca and local anaesthetics with skeletal muscle microsomes. J Cell Physiol l 1970; 75: 199-212
• 11 Seeman P. The membrane actions of anaesthetics and tranquilizers. Pharmacol Rev 1972; 24: 583-655
• 12 Low PS, Lloyd DH, Stein TM, Rogers JA. Calcium displacement by local anaesthetics. Dependence on pH and anaesthetic charge. J Biol Chem 1979; 254: 4119-4125
• 13 Loftfield RB, Eigner EA. Molecular order of participation of inhibitors (or activators) in biological systems. Sci 1969; 164: 305-308
• 14 Hofstee BH J. Non-inverted versus inverted plots in enzyme kinetics. Nature 1959; 184: 1296-1298
• 15 Narahashi T, Frazier DT. Site of action and active form of procaine in squid giant axon. J Pharmacol Exp Ther 1975; 197: 506-513
• 16 Khodorov B, Shishkova L, Paganov E, Revenko S. Inhibition of sodium currents in frog Ranvier nodes treated with local anaesthetics. Biochim Biophys Acta 1976; 433: 409-435
• 17 Mrose HE, Ritchie JE. Local anaesthetics: Do benzocaine and lidocaine act at the same site?. J Gen Physiol 1978; 71: 223-225
• 18 Jain MK, Eskow K, Kuchibhotla J, Colman RW. Correlation of inhibition of platelet aggregation by phenothiazines and local anaesthetics with their effects on a phospholipid bilayer. Thromb Res 1978; 13: 1067-1075
• 19 Godin DV, Au T, Garnett ME. Acetylcholinesterase: A probe for the study of antiarrhythmic drug membrane interactions. Biochim Biophys Acta 1978; 512: 388-396
• 20 Godin DV, Au T, Garnett ME. Membrane perturbational effects of antiarrhythmic drugs. J Mol Cell Cardiol 1979; 11: 261-274
• 21 Packham MA, Guccione MA, Greenberg JP, Kinlough-Rathbone RL, Mustard JF. Release of¹⁴C Serotonin during initial platelet changes induced by thrombin, collagen, or A23187. Blood 1977; 50: 915-926
• 22 Vanderhoek JY, Feinstein MB. Local anaesthetics, chlorpromazine and propranolol inhibit stimulus-activation of phospholipase A₂in human platelets. Molec Pharmacol 1979; 16: 171-180