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大鼠骨骼肌中两个普萘洛尔抗性(-)[125I]氰胍心安结合位点的定位与特性研究

Localization and characterization of two propranolol resistant (-) [125I]cyanopindolol binding sites in rat skeletal muscle.

作者信息

Molenaar P, Roberts S J, Kim Y S, Pak H S, Sainz R D, Summers R J

机构信息

Department of Pharmacology, University of Melbourne, Victoria, Australia.

出版信息

Eur J Pharmacol. 1991 Dec 17;209(3):257-62. doi: 10.1016/0014-2999(91)90179-t.

Abstract

Autoradiographic studies were performed in sections of rat gastrocnemius, plantaris and soleus muscle bundles with (-)-[125I]cyanopindolol (59-69 pM) in the presence of (-)-propranolol (1 microM) to block beta 1- and beta 2-adrenoceptors. Two distinct populations of binding sites remained, one evenly distributed over the muscle bundles and the other localized in discrete patches. Evenly distributed binding was highest in the soleus muscle and inhibited by (+/-)-, (-)- and (+)-alprenolol (20 microM), tertatolol (1 microM), BRL 37344 (2-20 microM), (-)-isoprenaline (100 microM), phentolamine (10 microM) and haloperidol (250 microM) but not ICI 118,551 (70 nM), CGP 20712A (100 nM), (+)-isoprenaline (100 microM), pindolol (2 microM), cimaterol (100 microM) or serotonin (10 microM). Stereoselectivity for the optical isomers of alprenolol was displayed in the soleus muscle only. Highly localized binding was inhibited by serotonin (10 microM), (-)- and (+)-isoprenaline (100 microM) and phentolamine (10 microM).

摘要

在大鼠腓肠肌、跖肌和比目鱼肌束切片中进行放射自显影研究,使用(-)-[125I]氰基吲哚洛尔(59 - 69 pM),同时存在(-)-普萘洛尔(1 microM)以阻断β1和β2肾上腺素能受体。仍存在两个不同的结合位点群体,一个均匀分布在肌束上,另一个定位于离散的斑块中。均匀分布的结合在比目鱼肌中最高,并被(±)-、(-)-和(+)-阿普洛尔(20 microM)、替他洛尔(1 microM)、BRL 37344(2 - 20 microM)、(-)-异丙肾上腺素(100 microM)、酚妥拉明(10 microM)和氟哌啶醇(250 microM)抑制,但不被ICI 118,551(70 nM)、CGP 20712A(100 nM)、(+)-异丙肾上腺素(100 microM)、吲哚洛尔(2 microM)、西马特罗(100 microM)或5-羟色胺(10 microM)抑制。仅在比目鱼肌中显示出对阿普洛尔光学异构体的立体选择性。高度局部化的结合被5-羟色胺(10 microM)、(-)-和(+)-异丙肾上腺素(100 microM)以及酚妥拉明(10 microM)抑制。

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