Department of Veterinary Internal Medicine, Faculty of Agriculture, Tottori University, Tottori, Japan.
Pharmacology. 2013;91(3-4):135-44. doi: 10.1159/000346269. Epub 2013 Jan 25.
BACKGROUND/AIMS: Imidazoline α2-adrenergic agents exert complex effects on mammalian platelet aggregation. Although non-adrenergic, imidazoline (I) receptors have been revealed in human platelets, there is limited information about imidazoline's action on platelet aggregation. This study aimed to investigate aggregatory and anti-aggregatory effects of various imidazoline or non-imidazoline α-adrenergic agents on rabbit platelets.
Aggregatory responses of agents on rabbit platelets were examined by turbidimetric method. Radioligand binding assay to platelet I1 and I2 receptors was performed using [(3)H]-clonidine and [(3)H]-idazoxan, respectively.
Aggregation was not induced by α-adrenoceptor agonists alone. Adrenaline and noradrenaline produced dose-dependent potentiation of ADP- or collagen-induced aggregation. Imidazoline adrenoceptor agonists clonidine and p-aminoclonidine also potentiated ADP-induced platelet aggregation. The α2-adrenoceptor antagonists and/or certain imidazoline adrenergic agents inhibited adrenaline-potentiated aggregation in a dose-dependent manner, whereas α1-adrenoceptor antagonists and non-imidazoline α-adrenergic agents were either ineffective or less effective in inhibiting adrenaline-potentiated aggregation. Rabbit platelets did not have I1 receptors, but had I2 receptors, indicating that adrenaline-potentiated platelet aggregation was inhibited by idazoxan, but not by imidazoline compounds clonidine and oxymetazoline.
CONCLUSIONS/IMPLICATIONS: These results demonstrated that α2-adrenoceptor-blocking agents and/or imidazoline α-adrenergic agents effectively inhibit adrenaline-potentiated platelet aggregation. It is proposed that imidazoline structure in part plays a role in the inhibition of adrenaline-potentiated aggregation.
背景/目的：咪唑啉 α2-肾上腺素能药物对哺乳动物血小板聚集产生复杂的影响。尽管咪唑啉（I）受体是非肾上腺素能的，但在人血小板中已发现了其存在，关于咪唑啉对血小板聚集的作用的信息有限。本研究旨在研究各种咪唑啉或非咪唑啉 α-肾上腺素能药物对兔血小板的聚集和抗聚集作用。
通过浊度法检测药物对兔血小板的聚集反应。使用 [(3)H]-可乐定和 [(3)H]-伊唑肟分别进行血小板 I1 和 I2 受体的放射配体结合测定。
α-肾上腺素受体激动剂单独不能诱导聚集。肾上腺素和去甲肾上腺素对 ADP 或胶原诱导的聚集产生剂量依赖性增强作用。咪唑啉肾上腺素受体激动剂可乐定和 p-氨基可乐定也增强了 ADP 诱导的血小板聚集。α2-肾上腺素受体拮抗剂和/或某些咪唑啉肾上腺素能药物以剂量依赖性方式抑制肾上腺素增强的聚集，而 α1-肾上腺素受体拮抗剂和非咪唑啉 α-肾上腺素能药物在抑制肾上腺素增强的聚集方面要么无效，要么效果较弱。兔血小板没有 I1 受体，但有 I2 受体，表明肾上腺素增强的血小板聚集被伊唑肟抑制，但被咪唑啉化合物可乐定和羟甲唑啉抑制。
结论/意义：这些结果表明，α2-肾上腺素受体阻断剂和/或咪唑啉 α-肾上腺素能药物可有效抑制肾上腺素增强的血小板聚集。据推测，咪唑啉结构部分参与了抑制肾上腺素增强的聚集。
