RECEPTOR-BINDING PROFILES OF AMILORIDE ANALOGS PROVIDE NO EVIDENCE FOR A LINK BETWEEN RECEPTORS AND THE NA+/H+ EXCHANGER, BUT INDICATE A COMMON STRUCTURE ON RECEPTOR PROTEINS
RECEPTOR-BINDING PROFILES OF AMILORIDE ANALOGS PROVIDE NO EVIDENCE FOR A LINK BETWEEN RECEPTORS AND THE NA+/H+ EXCHANGER, BUT INDICATE A COMMON STRUCTURE ON RECEPTOR PROTEINS
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DOI：
10.3109/10799899109064686
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发表时间：
1991-01-01
期刊：
影响因子：
--
通讯作者：
SOUDIJN, W
中科院分区：
文献类型：
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作者：
GARRITSEN, A;IJZERMAN, AP;SOUDIJN, W
阿米洛利及其类似物影响放射性配体与腺苷-A1受体的结合。在本文中，这种效果的特异性进行了研究，通过生成受体结合档案阿米洛利及其类似物。进行有限的结构-活性关系研究，以探讨抑制受体结合阿米洛利类似物和这些化合物对Na+转运，特别是Na+/H+交换的影响之间的关系。阿米洛利、苯扎米尔和5 '-（N，N-二甲基）阿米洛利（HMA）的受体结合特性表明，这些化合物影响多种受体，并且没有一种化合物对这些受体中的任何一种具有高度选择性。SAR研究表明，受体与Na+/H+交换或另一种阿米洛利敏感性离子转运系统之间的直接偶联不太可能抑制受体结合。偶联到所涉及的受体的信号转导系统和阿米洛利类似物的效力之间的相关性也是不存在的。受阿米洛利或其类似物影响的受体的不同性质表明受体和其他膜蛋白上广泛存在阿米洛利结合位点。
Amiloride and its analogues affect radioligand binding to the adenosine-A1 receptor. In this paper, the specificity of this effect is investigated by generating receptor binding profiles for amiloride and two of its analogues. A limited structure-activity relationships study is performed to probe the relationship between inhibition of receptor binding by amiloride analogues and the effects of these compounds on Na+ transport, in particular Na+/H+ exchange. The receptor binding profiles of amiloride, benzamil and 5'-(N,N-hexamethylene) amiloride (HMA) indicate that the compounds affect a variety of receptors and that none of the compounds is highly selective for any of these. The SAR study indicates that it is very unlikely that a direct coupling between receptors and Na+/H+ exchange or another amiloride-sensitive ion transport system is responsible for the inhibition of receptor binding. A correlation between the signal transduction systems coupled to the receptors involved and the potency of the amiloride analogues is also absent. The varying nature of the receptors, affected by amiloride or its analogues, suggests a wide-spread presence of an amiloride binding site on receptors and other membrane proteins.