Shimizu T, Kouketsu K
Research Division, Aichi Center, Japanese Red Cross, Blood Transfusion Service, Seto.
Jpn J Pharmacol. 1988 Feb;46(2):147-53. doi: 10.1254/jjp.46.147.
The present study was designed to understand the metabolism of 5-hydroxytryptamine (serotonin, 5HT), a dense granule constituent of platelets, in acidified platelet concentrates (PC) during in vitro storage in polyvinylchloride plastic containers at 22 degrees C. High-performance liquid chromatographic analysis showed that significant amounts of 5HT and its metabolites, 5-hydroxytryptophol and 5-hydroxyindole-3-acetic acid (5HIAA), were detected in the plasma of all PC stored for 3 days with a pH below 6.0, measured at 37 degrees C. PC with a platelet number over 7 x 10(10) cells maintained low PO2 values. Rapid fall in pH occurred in these PC with low PO2 values. The rate of lactate production of platelets increased several fold because of an insufficient oxygen supply to them. In PC with a sufficient supply of oxygen, the adenosine triphosphate (ATP) production rates were estimated to be 8 nmol/min/10(9) platelets. In PC acidified below pH 6.0, the oxidative phosphorylation nearly ceased, and glycolysis was also inhibited: ATP production rates averaged 1 nmol/min/10(9) platelets at 3-day storage. Numerous clusters of platelet aggregates were found in acidified PC, and platelets changed into spherical shapes with accompanying swelling. These platelets did not respond to adenosine triphosphate and failed to produce shrinking when suspended in hypotonic solutions. 5HT was not metabolized in acidified platelet-poor plasma. These data suggest that the metabolic activity of platelets was impaired when the pH of the PC fell below 6.0, leading to the release of platelet 5HT into the plasma. A substantial amount of 5HT might be metabolized by platelet monoamine oxidase into 5HIAA and 5-hydroxytryptophol.
本研究旨在了解5-羟色胺(血清素,5HT)的代谢情况,5HT是血小板致密颗粒的一种成分,在22℃下于聚氯乙烯塑料容器中体外储存期间,酸化血小板浓缩液(PC)中的5HT代谢情况。高效液相色谱分析表明,在37℃下测得pH低于6.0且储存3天的所有PC血浆中,均检测到大量的5HT及其代谢产物5-羟色醇和5-羟吲哚-3-乙酸(5HIAA)。血小板数量超过7×10¹⁰个细胞的PC维持较低的PO₂值。这些PO₂值低的PC中pH迅速下降。由于血小板的氧气供应不足,其乳酸生成速率增加了几倍。在氧气供应充足的PC中,三磷酸腺苷(ATP)生成速率估计为8 nmol/min/10⁹个血小板。在pH酸化至6.0以下的PC中,氧化磷酸化几乎停止,糖酵解也受到抑制:储存3天时ATP生成速率平均为1 nmol/min/10⁹个血小板。在酸化的PC中发现大量血小板聚集体簇,血小板变成球形并伴有肿胀。这些血小板对三磷酸腺苷无反应,悬浮于低渗溶液中时也不发生收缩。5HT在酸化的乏血小板血浆中不发生代谢。这些数据表明,当PC的pH降至6.0以下时,血小板的代谢活性受损,导致血小板5HT释放到血浆中。大量的5HT可能被血小板单胺氧化酶代谢为5HIAA和5-羟色醇。