Assessment of the central and peripheral alpha_2-adrenoceptor activities by using the platelet in inflammation.

本研究旨在探讨易燃犬血小板α _2-肾上腺素能受体活性与中枢和外周α _2-肾上腺素能受体活性的关系。为此，研究了各种咪唑啉类或非咪唑啉类α -肾上腺素能药物对犬血小板的聚集和抗聚集作用。然后，我们检测了α _2-肾上腺素能受体在血小板和脑膜上结合的变化，以及α _2-肾上腺素能受体介导的急性和慢性炎症犬的各种影响。本研究表明咪唑啉类α -肾上腺素能药物和/或α -肾上腺素受体阻滞剂能有效抑制犬肾上腺素增强的血小板聚集。因此，可以想象，肾上腺素增强的狗血小板聚集是由α _2-肾上腺素受体介导的。然而，咪唑啉受体可能作为非肾上腺素能结合位点存在于犬血小板上。非致死性内毒素注射引起的急性炎症使血小板中[^3H]育亨宾结合的Bmax降低，Kd增加，而在大脑皮层或延髓中，Bmax和Kd均降低。内毒素预处理可减少心血管疾病的影响，如心动过缓、低血压和由α _2-肾上腺素能受体激动剂引起的全身血管阻力增加。每周关节内注射角叉菜胶引起的慢性关节炎降低了血小板中育亨宾结合的[^3H] Bmax，并降低了大脑皮层和延髓中的Kd。这种慢性炎症降低了由α _2-肾上腺素能受体激动剂引起的镇静、心动过缓等作用，以及育亨宾抑制肾上腺素增强的血小板聚集的作用。这些结果表明，在急性和慢性炎症期间，中枢神经系统和外周系统的α _2-肾上腺素能受体活性受损。因此，血小板可能在一定程度上对炎症犬中枢神经系统或外周系统α _2-肾上腺素能受体变化的诊断具有重要意义。少

The purpose of this study was to investigate the relationship between the platelet alpha_2-adrenoceptor activity and the central and peripheral alpha_2-adrenoceptor activities in inflammable dogs. For this purpose, the aggregatory an anti-aggregatory effects of various imidazoline or non-imidazoline alpha-adrenergic agents on canine blood platelets werer examined. Then, we examined the changes in alpha_2-adrenoceptor binding on platelet and brain membranes, and the alpha_2-adrenoceptor mediated various effects in dogs that were inflamed acutely and chronically. This study showed that imidazoline alpha-adrenergic agents and/or alpha_2-adrenoceptor blocking agents inhibit effectively the epinephrine-potentiated platelet aggregation in dogs. Therefore, it is conceivable that epinephrine-potentiated platelet aggregation in dogs is mediated by alpha_2-adrenoceptors. However, imidazoline receptors as non-adrenergic binding sites may exist on canine blood platelet. Acute inflammation induced … More by a non-lethal endotoxin injection decreased Bmax of [^3H] yohimbine binding and increased Kd in platelets, whereas in either cerebral cortex or medulla oblongata, both Bmax and Kd decreased. Pretreatment with endotoxin diminished cardiovascular effects such as bradycardia, hypotention, and increase in systemic vascular resistance induced by alpha_2-adrenoceptor agonists. Chronic arthritis induced by weekly intra-articular injection of carrageenin decreased Bmax of [^3H] yohimbine binding in platelets, and decreased Kd in either cerebral cortex or medulla oblongata. This chronic inflammation reduced the sedation, bradycardia and other effects induced by alpha_2-adrenoceptor agonists, and the effect of yohimbine in inhibiting the epinephrine-potentiatedplatelet aggregation. These results suggest that alpha_2-adrenoceptor activity is impaired in the central nervous system as well as peripheral system during acute and chronic inflammations. Therefore, platelets may in part have a significance for diagnosis of alpha_2-adrenoceptor changes in the central nervous system or peripheral system in inflamed dogs. Less