碘化奎宁环基苯甲酸酯对映体与M3毒蕈碱受体的相互作用。

Interaction of iodinated quinuclidinyl benzilate enantiomers with M3 muscarinic receptors.

作者信息

Hiramatsu Y, Eckelman W C, Baum B J

机构信息

Clinical Investigations and Patient Care Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892.

出版信息

Life Sci. 1994;54(23):1777-83. doi: 10.1016/0024-3205(94)90116-3.

DOI:10.1016/0024-3205(94)90116-3

PMID:8196491

Abstract

We examined the interaction of 3-quinuclidinyl-4-iodobenzilate enantiomers, (RR)- and (SS)-IQNB, relatively receptor-active and -inactive, respectively, with M3-muscarinic receptors (mAChRs) in rat parotid acinar cells in vitro. This stereospecific antagonist pair has often been used for in vivo studies of mAChRs. There was a 16-fold difference in the ability of (RR)- and (SS)-IQNB to bind in vitro to mAChRs; Ki values estimated by competition with N-methylscopolamine were 5.3 and 84.2 nM, respectively. However, the ability of these antagonists to inhibit carbachol-stimulated inositol trisphosphate formation (Ki values determined by Schild analyses) was more similar, 16.3 and 47.7 nM, respectively for (RR)- and (SS)-IQNB. These data suggest that while it may be useful to employ this antagonist pair to evaluate some mAChR subtypes in vivo, it is difficult to use them in studies of M3-mAChRs.

摘要

我们在体外研究了3-喹核醇基-4-碘苯甲酸酯对映体，即（RR）-和（SS）-IQNB，它们分别相对具有受体活性和无活性，与大鼠腮腺腺泡细胞中的M3毒蕈碱受体（mAChRs）的相互作用。这一对立体特异性拮抗剂经常用于mAChRs的体内研究。（RR）-和（SS）-IQNB在体外与mAChRs结合的能力存在16倍的差异；通过与N-甲基东莨菪碱竞争估计的Ki值分别为5.3和84.2 nM。然而，这些拮抗剂抑制卡巴胆碱刺激的肌醇三磷酸形成的能力（通过Schild分析确定的Ki值）更为相似，（RR）-和（SS）-IQNB的Ki值分别为16.3和47.7 nM。这些数据表明，虽然使用这一对拮抗剂在体内评估某些mAChR亚型可能有用，但在M3-mAChRs的研究中很难使用它们。