The effect of inhaled anesthetics on the platelet aggregation and the ligand-binding affinity of the platelet thromboxane A2 receptor.
The mechanism by which anesthetics suppress platelet aggregation has not been elucidated. We determined the effects of halothane, enflurane, and isoflurane on human platelet aggregation induced by adenosine diphosphate (ADP), epinephrine, and a thromboxane A2 (TXA2) analog, and on ligand binding to the platelet TXA2 receptor. Halothane (2.6 mM) strongly suppressed ADP- and epinephrine-induced secondary aggregation of platelets, without significant alteration of primary aggregation. Platelet aggregation induced by a specific TXA2 agonist, (+)-9,11-epithia-11,12-methano-TXA2 (STA2), was suppressed by halothane, enflurane, and isoflurane in a concentration-dependent manner; the concentration of halothane, enflurane, and isoflurane which induced 50% inhibition (IC50) were 3.2, 12.3, and 15.7 mM, respectively (or 4.7, 9.8, and 24 minimum alveolar anesthetic concentration [MAC], respectively). The binding of a specific TXA2 receptor antagonist, 3H-S145, was significantly reduced by halothane (14-28 mM), but not by enflurane (20 mM) and isoflurane (20 mM). Scatchard analysis revealed that halothane (14 mM) increased Kd from 0.53 nM to 14.3 nM but did not alter Bmax significantly. These results indicate that halothane has a stronger suppressive effect on platelet aggregation than enflurane and isoflurane, and that the effect of halothane on platelet aggregation is due to reduction of the ligand-binding affinity of the platelet TXA2 receptor.
Hirakata
H
H
Department of Anesthesia, Kyoto University, Faculty of Medicine, Japan.
Ushikubi
F
F
Narumiya
S
S
Hatano
Y
Y
Nakamura
K
K
Mori
K
K
D000244:Adenosine Diphosphate / Q000494:pharmacology; D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004737:Enflurane / Q000008:administration & dosage / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D006221:Halothane / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D007530:Isoflurane / Q000008:administration & dosage / Q000494:pharmacology; D008024:Ligands; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D011982:Receptors, Prostaglandin / Q000187:drug effects; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors / Q000187:drug effects*; D013928:Thromboxane A2 / Q000819:agonists / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D014316:Tritium
D018685:Anesthetics, Inhalation; D001643:Bridged Bicyclo Compounds; D005229:Fatty Acids, Monounsaturated; D008024:Ligands; D010975:Platelet Aggregation Inhibitors; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D014316:Tritium; C056566:S 145; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; C037866:STA 2; D004737:Enflurane; D007530:Isoflurane; D006221:Halothane; D004837:Epinephrine