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磷酸肌醇代谢在肾上腺素增强ADP诱导的兔血小板聚集中的作用。

Involvement of phosphoinositide metabolism in potentiation by adrenaline of ADP-induced aggregation of rabbit platelets.

作者信息

Lalau Keraly C, Vickers J D, Kinlough-Rathbone R L, Mustard J F

出版信息

Biochem J. 1987 Mar 15;242(3):841-7. doi: 10.1042/bj2420841.

DOI:10.1042/bj2420841
PMID:3036103
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1147786/
Abstract

Changes in phosphoinositide metabolism were examined in washed rabbit platelets stimulated with 0.5 microM-ADP, 50 microM-adrenaline, or ADP and adrenaline in combination. Adrenaline does not stimulate platelet aggregation when used alone, but does potentiate aggregation stimulated by ADP. In platelets prelabelled with [32P]Pi and [3H]glycerol, adrenaline was found to potentiate the ADP-induced changes in platelet phospholipids, causing larger increases in the amount and labelling of phosphatidylinositol 4-phosphate (PIP) and phosphatidic acid than was observed with ADP alone. The combination of ADP and adrenaline did not produce a greater decrease in phosphatidylinositol 4,5-bisphosphate (PIP2) than was produced by ADP alone. In platelets prelabelled with [3H]inositol, adrenaline potentiated the increases in labelling of inositol phosphate and inositol bisphosphate stimulated by ADP; no increase in inositol trisphosphate labelling was detected with ADP alone or with the combination of ADP and adrenaline. Phentolamine, an alpha-adrenergic-receptor antagonist, blocked potentiation by adrenaline of ADP-induced changes in phosphoinositide metabolism. Propranolol and sotalol, beta-adrenergic-receptor antagonists, augmented the potentiation; this is consistent with the concept that the effect of adrenaline is mediated by beta-adrenergic receptors. The effect of adrenaline on phosphoinositide metabolism appears to be to potentiate the mechanisms by which ADP causes turnover of PIP and possibly degradation of PI, rather than the mechanism by which PIP2 is decreased.

摘要

研究了用0.5微摩尔/升二磷酸腺苷(ADP)、50微摩尔/升肾上腺素或ADP与肾上腺素联合刺激洗涤后的兔血小板时磷酸肌醇代谢的变化。单独使用肾上腺素时不会刺激血小板聚集,但会增强由ADP刺激引起的聚集。在用[32P]无机磷酸盐(Pi)和[3H]甘油预标记的血小板中,发现肾上腺素会增强ADP诱导的血小板磷脂变化,导致磷脂酰肌醇4-磷酸(PIP)和磷脂酸的量及标记量的增加幅度大于单独使用ADP时观察到的情况。ADP与肾上腺素的组合对磷脂酰肌醇4,5-二磷酸(PIP2)的减少幅度并不比单独使用ADP时更大。在用[3H]肌醇预标记的血小板中,肾上腺素增强了由ADP刺激引起的肌醇磷酸和肌醇二磷酸标记量的增加;单独使用ADP或ADP与肾上腺素组合时均未检测到肌醇三磷酸标记量的增加。酚妥拉明,一种α-肾上腺素能受体拮抗剂,可阻断肾上腺素对ADP诱导的磷酸肌醇代谢变化的增强作用。普萘洛尔和索他洛尔,β-肾上腺素能受体拮抗剂,则增强了这种增强作用;这与肾上腺素的作用是由β-肾上腺素能受体介导的这一概念相符。肾上腺素对磷酸肌醇代谢的作用似乎是增强ADP导致PIP周转以及可能导致磷脂酰肌醇(PI)降解的机制,而不是导致PIP2减少的机制。

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引用本文的文献

1
Synergism between thrombin and adrenaline (epinephrine) in human platelets. Marked potentiation of inositol phospholipid metabolism.凝血酶与肾上腺素在人血小板中的协同作用。肌醇磷脂代谢的显著增强。
Biochem J. 1988 Jul 15;253(2):581-6. doi: 10.1042/bj2530581.

本文引用的文献

1
A COMPARISON OF PLATELET AGGREGATION PRODUCED BY SEVEN COMPOUNDS AND A COMPARISON OF THEIR INHIBITORS.七种化合物所产生的血小板聚集的比较及其抑制剂的比较。
J Clin Pathol. 1964 May;17(3):275-81. doi: 10.1136/jcp.17.3.275.
2
Responses of rabbit platelets to adrenaline induced by other agonists.兔血小板对其他激动剂诱导的肾上腺素的反应。
Thromb Res. 1981;21(4-5):413-24. doi: 10.1016/0049-3848(81)90142-0.
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Changes in phosphatidylinositol-4,5-bisphosphate 10 seconds after stimulation of washed rabbit platelets with ADP.用二磷酸腺苷刺激洗涤后的兔血小板10秒后磷脂酰肌醇-4,5-二磷酸的变化。
Blood. 1982 Dec;60(6):1247-50.
4
Secretagogue-induced formation of inositol phosphates in rat exocrine pancreas. Implications for a messenger role for inositol trisphosphate.促分泌素诱导大鼠外分泌胰腺中肌醇磷酸的形成。对肌醇三磷酸信使作用的启示。
Biochem J. 1984 Apr 15;219(2):655-9. doi: 10.1042/bj2190655.
5
Accumulation of the inositol phosphates in thrombin-stimulated, washed rabbit platelets in the presence of lithium.在锂存在的情况下,凝血酶刺激的洗涤兔血小板中肌醇磷酸的积累。
Biochem J. 1984 Dec 1;224(2):399-405. doi: 10.1042/bj2240399.
6
Relationship between inositol polyphosphate production and the increase of cytosolic free Ca2+ induced by vasopressin in isolated hepatocytes.离体肝细胞中肌醇多磷酸生成与血管加压素诱导的胞质游离钙离子增加之间的关系。
J Biol Chem. 1984 May 10;259(9):5574-84.
7
Mammalian platelet adrenoceptors.哺乳动物血小板肾上腺素能受体。
Br J Pharmacol. 1984 Jan;81(1):91-102. doi: 10.1111/j.1476-5381.1984.tb10748.x.
8
Thyrotropin-releasing hormone-stimulated [3H]inositol metabolism in GH3 pituitary tumor cells. Studies with lithium.促甲状腺激素释放激素刺激GH3垂体瘤细胞中[3H]肌醇的代谢。锂的研究。
Mol Pharmacol. 1984 Mar;25(2):201-8.
9
Differential activation of phosphatidylinositol deacylation and a pathway via diphosphoinositide in macrophages responding to zymosan and ionophore A23187.巨噬细胞在对酵母聚糖和离子载体A23187作出反应时磷脂酰肌醇脱酰作用及经由二磷酸肌醇的一条途径的差异激活。
J Biol Chem. 1984 Mar 10;259(5):3111-6.
10
ADP-induced changes in [32P]phosphate labeling of phosphatidylinositol-4,5-bisphosphate in washed rabbit platelets made refractory by prior ADP stimulation.在经预先ADP刺激而变得不应性的洗涤兔血小板中,ADP诱导的磷脂酰肌醇-4,5-二磷酸的[32P]磷酸盐标记变化。
Biochem Biophys Res Commun. 1983 Jun 15;113(2):483-90. doi: 10.1016/0006-291x(83)91751-5.