Propofol inhibits human platelet aggregation induced by proinflammatory lipid mediators.
Lysophosphatidic acid (LPA), platelet-activating factor (PAF), and thromboxane A(2) are proinflammatory lipid mediators that activate surface receptors on platelets, producing increased intracellular calcium, which is necessary for aggregation. We investigated propofol's effect on platelet aggregation and intracellular calcium mobilization caused by these three agonists. Platelets from human volunteers were incubated in buffers containing LPA (1 microM), U46619 (thromboxane A(2) analog; 1 microM), or PAF (10 nM). Propofol emulsion or 2,6-diisopropylphenol (propofol without fat emulsion) dissolved in ethanol was added to achieve concentrations of propofol used clinically: 5 or 10 microg/mL. After 2 min, aggregation or intracellular calcium concentrations were measured with optical techniques. Propofol emulsion and propofol in ethanol produced similar inhibition of platelet aggregation induced by LPA, PAF, and U46619 in a dose-dependent fashion. LPA, PAF, and U46619 each caused significant increases in intracellular calcium that were not modified by propofol. Because propofol does not significantly alter intracellular calcium increases caused by receptor activation, inhibition appears to act distal to platelet receptors, inositol phosphate 3, and phospholipase C. Because the three lipid mediators play a key role in inflammation, their inhibition by propofol might be clinically important.
Fourcade
Olivier
O
Service d'Anesthésie-Réanimation, Hôpital Purpan, University of Toulouse, Place du Docteur Baylac, 31059 Toulouse Cedex, France. fourcade.o@chu-toulouse.fr
Simon
Marie-Françoise
MF
Litt
Lawrence
L
Samii
Kamran
K
Chap
Hugues
H
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000097:blood; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D008246:Lysophospholipids / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D015742:Propofol / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000187:drug effects; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000494:pharmacology
D018686:Anesthetics, Intravenous; D018836:Inflammation Mediators; D008246:Lysophospholipids; D010972:Platelet Activating Factor; D011956:Receptors, Cell Surface; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D002118:Calcium; D015742:Propofol