Effects of barbiturates on human platelet aggregation differ depending on their chemical structures.
The effects of barbiturates on human platelet function are not fully understood. Since we have already revealed the effects and mechanisms of thiopental, thiamylal, and pentobarbital in platelets, the present study attempted to elucidate (i) the effects of other barbiturates on human platelet aggregation, (ii) the underlying mechanisms, and (iii) the structure-function relationship of barbiturates in platelets. Barbiturates, including amobarbital, butalbital, secobarbital, barbital, phenobarbital, metharbital, and primidone, were examined. Human platelet aggregation induced by adenosine diphosphate (ADP), epinephrine, and (+)-9,11-epithia-11,12-methano-thromboxane A2 (STA2), a thromboxane A2 analog, was measured using an 8-channel light-transmission aggregometer. The cytosolic free calcium concentration ([Ca2+]i) was measured by fluorometer using fura-2 loaded platelets. Inositol 1,4,5-trisphosphate (IP3) formation induced by STA2 was determined by a commercially available IP3 assay kit. Amobarbital, butalbital, and secobarbital suppressed ADP-, epinephrine- and STA2-induced platelet aggregation and the STA2-induced [Ca2+]i increase, even when Ca2+ influx was blocked by Ni2+. However, they did not affect STA2-induced IP3 formation. Barbital, phenobarbital, metharbital, and primidone (up to 1 mM) had no effect on ADP- and epinephrine-induced platelet aggregation. Thus, we conclude that amobarbital, butalbital, and secobarbital inhibit platelet aggregation by suppressing [Ca2+]i increase without affecting IP3 formation. However, these antiaggregatory effects may not have clinical importance, since the barbiturate concentrations used were higher than clinically relevant ones. The other tested barbiturates had no effects on platelet aggregation. The data indicate that the effects of barbiturates on platelet aggregation differ depending on their chemical structures.
Sato
Masami
M
Department of Anesthesia, Kyoto University Hospital, Sakyo-ku, Kyoto 606-8507, Japan.
Hirakata
Hideo
H
Ikeda
Masahiro
M
Fukuda
Kazuhiko
K
D000328:Adult; D001463:Barbiturates / Q000737:chemistry* / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects* / Q000502:physiology; D013329:Structure-Activity Relationship
D001463:Barbiturates; D002118:Calcium