Subtype specificity of the muscarinic receptor-stimulated GTPase response in the rat cortex.
Subtype specificity of the muscarinic receptor-stimulated GTPase response in the rat cortex.
复制标题
大鼠皮质中毒蕈碱受体刺激的 GTP 酶反应的亚型特异性。
DOI：
10.1016/0304-3940(90)90803-h
复制
发表时间：
1990
影响因子：
2.5
通讯作者：
Hoss,W
中科院分区：
文献类型：
--
作者：
Ghodsi-Hovsepian,S;MesserJr,WS;Hoss,W
使用亚型选择性激动剂和拮抗剂来检查大鼠皮层中低KmGTdR应答的药理学。M2-选择性激动剂oxotremorine是脑中M1受体的弱部分激动剂，其刺激低KmGT活性，EC 50值为1.0 μM。氧震颤素几乎是一个完整的激动剂，并证明没有部分激动剂活性的存在下，最佳浓度的激动剂卡巴胆碱或氧震颤素-M，刺激所有的毒蕈碱反应。这些数据表明，GT3应答与M2受体有关。哌仑西平（M1-选择性）和AF-DX 116（M2-选择性）抑制氧化震颤素刺激的皮层GT3活性，IC 50值分别为4.0和2.2 μM。由于哌仑西平比AF-DX 116更有效地结合皮质中的毒蕈碱受体（Messer等人，医学化学杂志，32（1989）1164），M2受体比M1受体更有助于GT3应答。
Subtype selective agonists and antagonists were used to examine the pharmacology of the low-KmGTPase response in the rat cortex. The M2-selective agonist oxotremorine, which is a weak partial agonist for M1receptors in the brain, stimulated lowKmGTPase activity with an EC50value of 1.0 μM. Oxotremorine was nearly a full agonist and demonstrated no partial agonist activity in the presence of optimal concentrations of the agonists carbachol or oxotremorine-M, which stimulate all muscarinic responses. These data suggest that the GTPase response is associated with M2receptors. Pirenzepine (M1-selective) and AF-DX 116 (M2-selective) inhibited oxotremorine-stimulated GTPase activities in cortex with IC50values of 4.0 and 2.2 μM, respectively. Since pirenzepine is substantially more potent than AF-DX 116 for binding muscarinic receptors in the cortex (Messer et al., J. Med. Chem., 32 (1989) 1164), M2receptors contribute more to the GTPase response than M1receptors.