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

使用炎症中的血小板评估中枢和外周 α_2-肾上腺素受体活性。

• 批准号: 07660427
• 负责人: HIKASA Yoshiaki
• 金额: $ 1.47万
• 依托单位: Kitasato University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07660427/
• 关键词: Inflammation; Platelet; Central nervous system; Peripheral system; alpha_2-adrenoceptor

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

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及外周α_2-肾上腺素能受体活性的关系。为此目的，研究了各种咪唑啉或非咪唑啉α-肾上腺素能药物对犬血小板的聚集和抗聚集作用。然后，我们检测了急性和慢性炎症犬血小板和脑细胞膜上α_2-肾上腺素受体结合的变化，以及α_2-肾上腺素受体介导的各种效应。本研究表明咪唑啉类α-肾上腺素能药物和/或α_2-肾上腺素能受体阻滞剂能有效地抑制肾上腺素增强的狗血小板聚集。因此，肾上腺素增强犬血小板聚集可能是由α_2-肾上腺素受体介导的。然而，咪唑啉受体作为非肾上腺素能结合位点可能存在于犬血小板上。急性炎症诱导 ...更多信息 注射非致死性内毒素后，血小板中[^3H]育亨宾结合的Bmax降低，Kd增加，而在大脑皮质或延髓中，Bmax和Kd均降低。内毒素预处理可减轻α_2-肾上腺素受体激动剂引起的心血管效应，如心动过缓、收缩和全身血管阻力增加。每周关节内注射角叉菜胶诱导的慢性关节炎降低了血小板中[^3H]育亨宾结合的Bmax，降低了大脑皮质或延髓中的Kd。这种慢性炎症使α_2-肾上腺素能受体激动剂引起的镇静、心动过缓等作用减弱，并使育亨宾抑制肾上腺素增强的血小板聚集作用减弱。这些结果表明，在急性和慢性炎症时，中枢神经系统和外周系统的α_2-肾上腺素能受体活性均受到损害。因此，血小板对诊断炎症犬中枢神经系统或外周系统的α_2-肾上腺素能受体变化可能具有部分意义。少