Platelets as a marker of adrenergic and serotonergic receptors in dogs

血小板作为狗肾上腺素能和血清素能受体的标记

• 批准号: 11660313
• 负责人: HIKASA Yoshiaki
• 金额: $ 2.3万
• 依托单位: Tottori University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11660313/
• 关键词: Dog; Platelet; Adrenoceptor; Imidazoline receptor; Guanine nucleotide; Adrenaline; Serotonin; GTP binding protein; イダゾキサン; クロニジン; ヨヒンビン; アグマチン; 血小板凝集

The present study was conducted to investigate the platelet activity as a marker of adrenergic, non-adrenergic, and serotonergic receptors in dogs, based on previous findings that monoamine, and in particular 5-hydroxytryptamine in the brain, are involved in the regulation of α_2-adrenoceptor-mediated emesis. This study demonstrated that the α_<2A>-adrenoceptor subtype exists on canine platelets, and this type of receptors was involved in the mediation of adrenaline-potentiated platelet aggregation. The results of α_2-adrenoceptor binding and the α_2-adrenoceptor-mediated cardiovascular effects during canine endotoxin shock revealed that significant positive correlations were observed for reduced number of α_2-adrenoceptors between platelets and brain, and diminished cardiovascular effects of α_2-adrenoceptor agonists. Therefore, the α_<2A>-adrenoceptor activity was impaired in the central nervous system as well as in the peripheral vascular system during canine endotoxin shock. These results indicated that platelets may in part represent a good model which reflects the α_2-adrenoceptor changes in the central nervous system and peripheral vascular system during and after activation of sympatho-adrenal nerve activity. On the other hand, this study demonstrated that imidazol(in)e (I) structure has a role for inhibition of adrenaline-potentiated platelet aggregation in dogs, and that two subtypes of non-adrenergic I receptors, I_1 and I_2, exist on canine platelets. In addition, this study suggested that I_1 subtype was coupled with GTP-binding proteins, and I_2 was not coupled with those. Further studies may be required to investigate the function of I_1 and I_2 receptors as well as 5-HT receptors in canine platelets.

本研究在前人研究的基础上，探讨了血小板活性作为犬肾上腺素能、非肾上腺素能和肾上腺素能受体的标志物，即脑内单胺，特别是5-羟色胺参与α_2-肾上腺素能受体介导的呕吐的调节。本研究证实<2A>犬血小板上存在α-肾上腺素受体亚型，这种受体参与介导肾上腺素增强的血小板聚集。犬内毒素休克时α_2-肾上腺素受体结合与α_2-肾上腺素受体介导的心血管效应的研究结果表明，血小板和脑间α_2-肾上腺素受体数量的减少与α_2-肾上腺素受体激动剂心血管效应的减弱呈显著正相关。因此，<2A>犬内毒素休克时，中枢神经系统和外周血管系统的α-肾上腺素能受体活性均受到损害。这些结果表明，血小板可部分反映交感-肾上腺神经活动激活时和激活后中枢神经系统和外周血管系统α_2-肾上腺素能受体的变化。另一方面，本研究证实咪唑（in）e（I）结构对肾上腺素增强的犬血小板聚集有抑制作用，并证实犬血小板上存在两种非肾上腺素能I受体亚型I_1和I_2。此外，本研究还提示I_1亚型与GTP结合蛋白偶联，而I_2亚型与GTP结合蛋白不偶联。犬血小板I_1、I_2受体和5-HT受体的功能尚需进一步研究。

项目成果

Yoshiaki Hikasa, et al: "Platelet and brain α_2-adrenoceptors and cardiovascular sensitivity to agonists in dogs suffering from endotoxic shock"Fundamental and Clinical Pharmacology. 12 (5). 498-509 (1998)

Yoshiaki Hikasa 等人：“患有内毒素休克的狗的血小板和脑α_2-肾上腺素受体以及心血管对激动剂的敏感性”基础和临床药理学12(5)(1998)。

Yoshiaki Hikasa, et al: "Alpha adrenoceptor subtypes involved in the emetic action in dogs"Journal of Pharmacology and Experimental Therapeutics. 261 (2). 746-754 (1992)

Yoshiaki Hikasa 等人：“阿尔法肾上腺素受体亚型参与狗的催吐作用”药理学和实验治疗学杂志。

Yoshiaki Hikasa et al.: "Connective tissue-type mast cell leukemia in a dog"Journal of Veterinary Medical Science. 62・2. 187-190 (2000)

Yoshiaki Hikasa 等：“狗的结缔组织型肥大细胞白血病”《兽医医学杂志》62・2（2000 年）。

Yoshiaki Hikasa: "Central alpha-adrenoceptor subtypes involved in the emetic pathway in cats"European Journal of Pharmacology. 229・2-3. 241-251 (1992)

Yoshiaki Hikasa：“参与猫催吐途径的中枢α-肾上腺素受体亚型”欧洲药理学杂志229·2-3（1992）。

Kazuhito Itamoto et al.: "Quantitative electroencephalography of medetomidine, medetomidine-midazolam and medetomidine-midazolam-butorphanol in dogs"Journal of Veterinary Medicine, Series A. 49(in press). (2002)

Kazuhito Itamoto 等人：“犬中美托咪定、美托咪定-咪达唑仑和美托咪定-咪达唑仑-布托啡诺的定量脑电图”《兽医杂志》，系列 A.49（出版中）。