The Role of Carbohydrate Moiety in Alpha_1-adrenoceptors in Rat Heart : Composition with those of Beta_1-adrenoceptors (1988-1989).

碳水化合物部分在大鼠心脏α_1-肾上腺素受体中的作用：与β_1-肾上腺素受体的组成（1988-1989）。

• 批准号: 63570102
• 负责人: NAGATOMO Takafumi
• 金额: $ 1.34万
• 依托单位: Nigata University of Phermacy and Applied Life Sciences
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1988
• 资助国家: 日本
• 起止时间: 1988 至 1989
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-63570102/
• 关键词: alpha_1-Adrenoceptors; beta_1-adrenoceptors; Heart muscle membrane; ^3H-prazosin; ^3HーCGP12177; Heparin; Polymixin B; DNA; アドレナリンα_1-受容体; アドレナリン性β_1-受容体; ^3H-prazosin; ^3H-CGP12177; ヘパリン; アドレナリン性α_1受容体; ラット

The present study was designed to test the role of carbohydrate moiety in the alpha_1-adrenoceptors in rat heart membranes using the radioligand binding assay. The rat hearts were used and ^3H-prazosin and ^3H-CGP12177 were used as radioligands. Kd values of alpha_1- and beta_1-adrenoceptors obtained from Scatchard analysis using l ligand-l receptor model were 0.493<plus-minus>0.305 (alpha_1-) and 0.502<plus-minus>0.135 (beta_1-) nM, and in addition, Bmax values of those receptors were 29.8<plus-minus>18.8 (alpha_1-) and 9.0<plus-minus>0.9 (beta_1-) fmole/mg protein, respectively. The result obtained Scatchard analysis using l-ligand-2 receptor model showed biphasic curves and this implies that two binding sites of ^3H-prazosin in rat heart membrane were existed.The effect of polymeric effectors (polymixin B, heparin and DNA) on the ^3H-prazosin and ^3H-CGP12177 bindings to alpha_1-adrenoceptor and beta_1-adrenoceptors in rat heart membrane was also examined. Although no changes in values of Kd and Bmax of alpha_1-adrenoceptors by addition of these polymeric effectors in vitro was observed, polymixin B induced the high Kd values and heparin induced high Bmax values of beta_1-adrenoceptors of rat heart membranes. No changes in beta-adrenoceptors by the addition of DNA were observed.In conclusion, the present study suggest that different binding characteristics of each adrenoceptor may exist from results of the different effects of polymeric effectors. In addtion, the results obtained from rat heart muscle was different from these of rat brain. Thus, binding charaacteristics of alpha_1- and beta_1-adrenoceptors in rat heart may be different from those in brain.

本研究旨在使用放射性配体结合测定来测试碳水化合物部分在大鼠心脏膜的α1-肾上腺素受体中的作用。使用大鼠心脏并使用^ 3 H-哌唑嗪和^ 3 H-CGP12177作为放射性配体。使用l配体-l受体模型从斯卡查德分析获得的α_1-和β_1-肾上腺素受体的Kd值为0.493±0.305（α_1-）和0.502±0.135（β_1-）nM，此外，这些受体的Bmax值为29.8±18.8（α_1-）和 分别为 9.0±0.9 (beta_1-) fmole/mg 蛋白质。使用l-配体-2受体模型获得的Scatchard分析结果显示双相曲线，这意味着大鼠心膜中存在^3H-哌唑嗪的两个结合位点。聚合物效应物（多粘菌素B、肝素和DNA）对^3H-哌唑嗪和^3H-CGP12177与α_1-肾上腺素受体结合的影响和 还检查了大鼠心脏膜中的β1-肾上腺素受体。虽然体外添加这些聚合物效应物没有观察到α_1-肾上腺素受体的Kd和Bmax值发生变化，但多粘菌素B诱导大鼠心膜β_1-肾上腺素受体的高Kd值和肝素诱导高Bmax值。没有观察到添加DNA引起的β-肾上腺素受体的变化。总之，本研究表明，由于聚合物效应器的不同作用，可能存在每种肾上腺素受体不同的结合特征。此外，从大鼠心肌获得的结果与从大鼠大脑获得的结果不同。因此，大鼠心脏中α_1-和β_1-肾上腺素受体的结合特征可能与大脑中的不同。

项目成果

Tsuchihashi,H.: Japanese Journal of Pharmacology. 49. 11-19 (1989)

土桥，H.：日本药理学杂志。

長友 孝文 等: "ラット心筋膜α_1ー受容体における糖鎖の役割:β_1ー受容体との比較" 第65回日本薬理学会総会(1992年,仙台).

Takafumi Nagatomo等人：“糖链在大鼠心肌α_1-受体中的作用：与β_1-受体的比较”日本药理学会第65届年会（1992年，仙台）。

Nagatomo, T. Tsuchihashi, H., Maruyama, K., Kinami, J.: "The role of carbohydrate moiety in alpha_1-adrenoceptors in rat heart : Comparison with those of beta_1-adrenoceptors." The 65th Annual Meeting of Japanese Journal of Pharmacology. (1992)

Nagatomo, T. Tsuchihashi, H.、Maruyama, K.、Kinami, J.：“碳水化合物部分在大鼠心脏 α_1-肾上腺素受体中的作用：与 β_1-肾上腺素受体的比较。”