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

本研究旨在探讨易感犬血小板α_2受体活性与中枢和外周α_2受体活性的关系。为此，我们观察了不同咪唑啉或非咪唑啉类α-肾上腺素能药对犬血小板的抗聚集作用。然后，我们观察了急性和慢性炎症犬血小板和脑膜上α_2肾上腺素能受体结合的变化，以及α_2受体介导的各种作用。本研究表明，咪唑啉α-肾上腺素能药和/或α_2受体阻断剂能有效地抑制肾上腺素增强的犬血小板聚集。因此，可想而知，肾上腺素增强的犬血小板聚集是由α_2肾上腺素受体介导的。但犬血小板上可能存在咪唑啉受体作为非肾上腺素能结合部位。急性炎症诱导的…此外，注射非致死性内毒素降低了[~3H]育亨宾结合的Bmax，增加了血小板的Kd，而在大脑皮层和延髓，Bmax和Kd均降低。内毒素可减轻α_2肾上腺素能受体激动剂引起的心血管效应，如心动过缓、低血压和增加全身血管阻力。每周关节内注射角叉菜胶致慢性关节炎大鼠血小板[~(3 H)]育亨宾结合量Bmax降低，大脑皮层或延髓Kd降低。这种慢性炎症减少了α_2-肾上腺素能受体激动剂引起的镇静、心动过缓和其他作用，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，急性和慢性炎症时中枢神经系统和外周系统的α_2肾上腺素能受体活动均受损。因此，血小板可能对炎症犬中枢神经系统或外周系统的α_2肾上腺素能受体改变有一定的诊断意义。较少

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