Study of properties of high and low affinity binding sites in beta-adrenoceptors

β-肾上腺素受体高亲和力和低亲和力结合位点特性的研究

• 批准号: 02671015
• 负责人: KOIKE Katsuo
• 金额: $ 1.6万
• 依托单位: Toho University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02671015/
• 关键词: Beta-adrenoceptor; Partial agonist; Stereoisomer; High affinity site; Low affinity site; Guinea-pig taeaia caecum; Rabbit ciliary body; モルモット盲腸組; 構造最適化; β故アドレナリン受容体; サイクリックAMP; モルモット盲腸紐; ウサギ毛様体筋; βーアドレナリン受容体; 活性作用; 拮抗作用

The stereoselectivities of beta-adrenergic partial agonists for the high and low affinity binding sites of beta-adrenoceptors were studied. Our results suggest that the high affinity binding site of beta-adrenoceptors is more stereoselective than the low affinity binding site in the guinea-pig taenia caecum. The pA_2-Values of the s(-)-isomers of befunolol and carteolol against S(-)-isoprenaline, which were calculated from the shift of each concentration-response curve in increasing cyclic AMP levels, were significantly larger than those of the R(+)-isomers in the guinea-pig taenia caecum, while the pA_2-values of the S(-)-isomers were not significantly larger than those of the R(+)-isomers in the rabbit ciliary body. The pki-values determined from the binding experiments were in good agreement with the pA_2-values from the increases in cyclic AMP levels. These results suggest that the high affinity binding site of beta-adrenoceptors in the guinea-pig taenia caecum may be able to discriminate stereoselecticity between the R(+)-and S(-)-isomers, while in the rabbit ciliary body there is no stereoselectivity between the two enantiomers.

研究了β-肾上腺素能部分激动剂对β-肾上腺素能受体高、低亲和力结合位点的立体选择性。我们的研究结果表明，β-肾上腺素受体的高亲和力结合位点比低亲和力结合位点在豚鼠盲肠中具有更大的立体选择性。贝福洛尔和卡替洛尔的S（-）-异构体对S（-）-异丙肾上腺素的pA_2值（由环腺苷酸浓度增加时各浓度-反应曲线的位移计算）明显大于R（+）-异构体。而在兔睫状体中，S（-）-异构体的pA_2值并不明显大于R（+）-异构体。从结合实验中确定的pki值与从环AMP水平的增加中确定的pA_2值非常一致。这些结果表明，β-肾上腺素能受体在豚鼠盲肠带中的高亲和力结合位点可能能够区分R（+）-和S（-）-异构体之间的立体选择性，而在兔睫状体中，两种对映体之间没有立体选择性。

项目成果

Koike, K. et al: "Comparison of interactions of R-(+)- and S-(-)-isomers of beta-adrenergic partial agonists, befunolol and carteolol, with high affinity site of beta-adrenoceptors in isolated rabbit ciliary body and guinea-pig taenia caeci." Can. J. Phys

Koike, K. 等人：“β-肾上腺素能部分激动剂、苯呋洛尔和卡替洛尔的 R-( )- 和 S-(-)-异构体与离体兔睫状体中 β-肾上腺素受体高亲和力位点的相互作用的比较

Takayanagi,I.et al.: "Effects of the R(+)-and S(-)-isomers of β-adrenoceptor blockers with intrinsic sympathomimetic activity,befunolol and carteolol,on rabbit intraocular pressure" Can.J.Physiol.Pharmacol.69. 1243-1245 (1991)

Takayanagi,I.et al.：“具有内在拟交感活性的 β-肾上腺素受体阻滞剂的 R(+)-和 S(-)-异构体，苯酚洛尔和卡替洛尔，对兔眼内压的影响”Can.J.Physiol.Pharmacol .69.1243-1245（1991）

Kotke,K.et al.: "Comparison of interactions of R(+)-and S(-)-isomers of β-adrenergic partial agonists,befunolol and carteolol,with high affinity site of β-adrenoceptors in isolated rabbit ciliary body and guinea-pig taenia caeci" Can.J.Physiol.Pharmacol.6

Kotke, K. 等人：“β-肾上腺素能部分激动剂、苯酚洛尔和卡替洛尔的 R(+)-和 S(-)-异构体与离体兔睫状体中 β-肾上腺素受体高亲和力位点的相互作用的比较，以及豚鼠盲肠带绦虫”Can.J.Physiol.Pharmacol.6

Katsuo KOIKE: "Comparison of interaction of Rー(+)ーand S(-)ーisomers of βーadrenergic partial agonists,befundol and cartedol,with affinity site of βーadrenoceptors in isolated rabbit ciliany body and guineaーpig taenia caeci" Can.J.Physiol.Pharmacol.69. 951-95

Katsuo KOIKE：“β-肾上腺素能部分激动剂、befundol 和 cartedol 的 R-(+)- 和 S(-)- 异构体与离体兔纤毛体和豚鼠盲肠绦虫中 β-肾上腺素受体亲和位点的相互作用的比较” Can.J.Physiol.Pharmacol.69。

Takayanagi,I.et al.: "Stereoselectivity in beta-adrenomimetic and beta-adrenolytic actions of carteolol,a beta-adrenoceptor blocker with intvinsic sympathomimetic action in guinea-pig taenia caecum" Gen.Pharmacol.21. 309-312 (1990)

Takayanagi,I.et al.：“卡替洛尔的 β- 拟肾上腺素和 β- 肾上腺素溶解作用的立体选择性，卡替洛尔是一种 β- 肾上腺素受体阻滞剂，在豚鼠盲肠带内具有拟交感神经作用”Gen.Pharmacol.21。