Lalau Keraly C, Vickers J D, Kinlough-Rathbone R L, Mustard J F
Biochem J. 1987 Mar 15;242(3):841-7. doi: 10.1042/bj2420841.
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.
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。