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模拟血小板凝块形成的生物化学能量学。凝血酶、二磷酸腺苷和肾上腺素对细胞内和细胞外腺嘌呤核苷酸动力学的影响。

Biochemical energetics of simulated platelet plug formation. Effect of thrombin, adenosine diphosphate, and epinephrine on intra- and extracellular adenine nucleotide kinetics.

作者信息

Karpatkin S, Langer R M

出版信息

J Clin Invest. 1968 Sep;47(9):2158-68. doi: 10.1172/JCI105902.

DOI:10.1172/JCI105902
PMID:5675431
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC297377/
Abstract

Washed human platelets were incubated in a modified Ringer's solution, pH 7.1, at 37 degrees C for 1 hr. Intracellular basal levels for glycogen, adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), and orthophosphate were 31.1, 2.52, 1.39, 0.36, and 1.2 mumoles/ml of platelets, respectively. Extracellular ATP, ADP, and AMP remained fairly constant and represented 4, 2, and 4% of total adenine nucleotide content. Total adenine nucleotide content remained unchanged during the period of control incubation. Glycogen depletion was 17.8 mumoles/ml at the end of 1 hr; lactate production was 20.7 mumoles/ml per hr. In the presence of glucose, lactate production increased 100%, and glycogen depletion was spared 13%. Approximately 55% of glucose or glycogen fuel was converted to lactate. The agglutinating agents, thrombin, ADP, and epinephrine, resulted in increased glycogen depletion and lactate production both in the presence and absence of glucose. The effect of thrombin was greater than epinephrine. The effect of epinephrine was greater than ADP. All three agglutinating agents resulted in loss of high energy phosphates (net decline in adenine nucleotides) with release of adenine nucleotides into the extracellular environment. The effect of thrombin was greater than ADP. The effect of ADP was greater than epinephrine. In experiments with ADP addition, significant quantities of ADP were converted to AMP extracellularly. In experiments with thrombin and epinephrine appreciable quantities of extracellular orthophosphate were taken up by plateletes and could not be accounted for by changes in intracellular orthophosphate or adenine nucleotide. Sufficient ADP was released during exposure to thrombin and epinephrine to account for platelet agglutination. Changes in intracellular adenine nucleotides and orthophosphate could be correlated with the activation of regulator glycogenolytic and glycolytic enzymes.

摘要

洗涤后的人血小板在pH 7.1的改良林格氏溶液中于37℃孵育1小时。血小板内糖原、三磷酸腺苷(ATP)、二磷酸腺苷(ADP)、一磷酸腺苷(AMP)和正磷酸盐的基础水平分别为31.1、2.52、1.39、0.36和1.2微摩尔/毫升血小板。细胞外ATP、ADP和AMP保持相当恒定,分别占总腺嘌呤核苷酸含量的4%、2%和4%。在对照孵育期间,总腺嘌呤核苷酸含量保持不变。1小时结束时糖原消耗为17.8微摩尔/毫升;乳酸生成量为每小时20.7微摩尔/毫升。在有葡萄糖存在的情况下,乳酸生成增加100%,糖原消耗减少13%。大约55%的葡萄糖或糖原燃料转化为乳酸。凝集剂凝血酶、ADP和肾上腺素在有或没有葡萄糖存在的情况下均导致糖原消耗增加和乳酸生成增加。凝血酶的作用大于肾上腺素。肾上腺素的作用大于ADP。所有三种凝集剂均导致高能磷酸盐损失(腺嘌呤核苷酸净减少),同时腺嘌呤核苷酸释放到细胞外环境中。凝血酶的作用大于ADP。ADP的作用大于肾上腺素。在添加ADP的实验中,大量ADP在细胞外转化为AMP。在凝血酶和肾上腺素的实验中,大量细胞外正磷酸盐被血小板摄取,无法通过细胞内正磷酸盐或腺嘌呤核苷酸的变化来解释。在接触凝血酶和肾上腺素期间释放的ADP足以解释血小板凝集。细胞内腺嘌呤核苷酸和正磷酸盐的变化与调节性糖原分解酶和糖酵解酶的激活相关。

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