Kerry R, Scrutton M C, Wallis R B
Br J Pharmacol. 1984 Jan;81(1):91-102. doi: 10.1111/j.1476-5381.1984.tb10748.x.
Mammalian platelets vary widely in their responses to catecholamines in part because these agonists can act via excitatory alpha- and inhibitory beta-adrenoceptors. In the absence of antagonists, adrenaline enhances the response of rabbit platelets to an excitatory agonist, e.g. adenosine-5'-O-(1-thiodiphosphate) (ADP-alpha-s) acting at another receptor, but has no effect on the response of rat or guinea pig platelets to such an agonist. In the presence of a beta-adrenoceptor antagonist, adrenaline enhances the response of rat, but not guinea-pig platelets to ADP-alpha-S and the extent of the enhanced effect on rabbit platelets is increased. In the presence of an alpha-adrenoceptor antagonist, adrenaline inhibits the response of rabbit and rat platelets to ADP-alpha-S but has no such effect on the response of guinea-pig platelets. Studies using selective agonists and antagonists demonstrate that the excitatory response of rat platelets to adrenaline is mediated by an alpha 2-adrenoceptor, and the inhibitory response of rabbit platelets to adrenaline by a beta 2-adrenoceptor as is the case in other species which have been examined. The mean alpha 2-adrenoceptor density on human, rabbit, rat and guinea-pig platelets as assessed using [3H]-yohimbine as radioligand is obtained as 258, 270, 42 and less than 10 receptors per platelet. The mean beta 2-adrenoceptor density on human, rabbit, rat and guinea-pig platelets as assessed using (-)-[125I]-iodocyanopindolol is obtained as 66, 14, 41 and less than 5 receptors per platelet. The nature of the effect of adrenaline on the response of mammalian platelets to other excitatory agonists, e.g. ADP-alpha-S, appears therefore to be largely determined by the absolute number of alpha 2-adrenoceptors and by the relative content of alpha 2- and beta 2-adrenoceptors on these cells for the species which have been examined in this analysis.
哺乳动物血小板对儿茶酚胺的反应差异很大,部分原因是这些激动剂可通过兴奋性α-肾上腺素能受体和抑制性β-肾上腺素能受体发挥作用。在没有拮抗剂的情况下,肾上腺素可增强兔血小板对兴奋性激动剂(如作用于另一种受体的腺苷-5'-O-(1-硫代二磷酸)(ADP-α-s))的反应,但对大鼠或豚鼠血小板对该激动剂的反应没有影响。在存在β-肾上腺素能受体拮抗剂的情况下,肾上腺素可增强大鼠而非豚鼠血小板对ADP-α-S的反应,并且对兔血小板增强作用的程度增加。在存在α-肾上腺素能受体拮抗剂的情况下,肾上腺素可抑制兔和大鼠血小板对ADP-α-S的反应,但对豚鼠血小板的反应没有这种作用。使用选择性激动剂和拮抗剂的研究表明,大鼠血小板对肾上腺素的兴奋性反应由α2-肾上腺素能受体介导,兔血小板对肾上腺素的抑制性反应由β2-肾上腺素能受体介导,这与已研究的其他物种情况相同。使用[3H]-育亨宾作为放射性配体评估,人、兔、大鼠和豚鼠血小板上的平均α2-肾上腺素能受体密度分别为每血小板258、270、42和少于10个受体。使用(-)-[125I]-碘氰吲哚洛尔评估,人、兔、大鼠和豚鼠血小板上的平均β2-肾上腺素能受体密度分别为每血小板66、14、41和少于5个受体。因此,肾上腺素对哺乳动物血小板对其他兴奋性激动剂(如ADP-α-S)反应的影响性质,在很大程度上似乎取决于α2-肾上腺素能受体的绝对数量以及这些细胞上α2-和β2-肾上腺素能受体的相对含量,这是针对本分析中所研究的物种而言的。