Koutouzov S, Cothenet-Vernoux L, Marche P, Dausse J P
Thromb Res. 1985 Oct 15;40(2):147-59. doi: 10.1016/0049-3848(85)90325-1.
This work was designed to investigate the influence of rat platelet adrenoceptors on the early thrombin-induced serotonin release. In washed platelets prelabeled with [3H]-serotonin, adrenaline and isoproterenol both inhibited, in a dose-dependent manner, the early thrombin-induced secretion of serotonin. Inhibitory responses of both adrenaline and isoproterenol were blocked in the presence of beta-adrenoceptor antagonists, suggesting that the catecholamine acted solely through beta-adrenoceptors. However, isoproterenol inhibited the thrombin-induced serotonin release to a much greater extent than the catecholamine, suggesting that the alpha 2-component of adrenaline might account for the difference observed between the two compounds. Our observation that selective alpha 2-adrenoceptor antagonists as yohimbine and rauwolscine potentiated the inhibitory effect of adrenaline to a level close to that observed with isoproterenol, lends support to the above hypothesis. This latter result suggested that, conversely, alpha 2-adrenergic compounds might exert a counteracting effect on a full beta-adrenoceptor mediated inhibition. Although synthetic alpha 2-adrenergic agents failed to influence isoproterenol inhibitory effect, our study shows that prestimulation of beta-adrenoceptors by isoproterenol, followed by addition of adrenaline or noradrenaline markedly diminished the inhibitory effect of isoproterenol to a level close to that which characterized the inhibition observed with catecholamines, when tested alone. Our work favours the hypothesis that, in rat platelets, early after platelet stimulation, catecholamines might counteract a beta-adrenoceptor- mediated inhibition, through alpha 2-adrenoceptor sites.
本研究旨在探讨大鼠血小板肾上腺素能受体对凝血酶诱导的早期5-羟色胺释放的影响。在用[3H]-5-羟色胺预标记的洗涤血小板中,肾上腺素和异丙肾上腺素均以剂量依赖的方式抑制凝血酶诱导的5-羟色胺早期分泌。在β-肾上腺素能受体拮抗剂存在的情况下,肾上腺素和异丙肾上腺素的抑制反应均被阻断,这表明儿茶酚胺仅通过β-肾上腺素能受体起作用。然而,异丙肾上腺素比儿茶酚胺更能抑制凝血酶诱导的5-羟色胺释放,这表明肾上腺素的α2成分可能是造成这两种化合物之间差异的原因。我们观察到,像育亨宾和萝芙木碱这样的选择性α2-肾上腺素能受体拮抗剂可将肾上腺素的抑制作用增强至接近异丙肾上腺素的水平,这支持了上述假设。后一结果表明,相反,α2-肾上腺素能化合物可能对完全由β-肾上腺素能受体介导的抑制作用产生抵消作用。尽管合成的α2-肾上腺素能药物未能影响异丙肾上腺素的抑制作用,但我们的研究表明,先用异丙肾上腺素预刺激β-肾上腺素能受体,然后加入肾上腺素或去甲肾上腺素,当单独测试时,异丙肾上腺素的抑制作用会明显减弱至接近儿茶酚胺抑制作用的水平。我们的研究支持这样一种假设,即在大鼠血小板中,血小板刺激后早期,儿茶酚胺可能通过α2-肾上腺素能受体位点抵消β-肾上腺素能受体介导的抑制作用。