Houghtling R A, Dávila-García M I, Kellar K J
Department of Pharmacology, Georgetown University School of Medicine, Washington, D. C. 20007, USA.
Mol Pharmacol. 1995 Aug;48(2):280-7.
Epibatidine is an alkaloid that was first isolated from the skin of the Ecuadoran frog Epipedobates tricolor by Daly et al. [J. Am. Chem. Soc. 102:803-836 (1980)] and was found to have very high affinity for neuronal nicotinic receptors, where it acts as a potent agonist. Here we have measured and characterized the binding of (+/-)(-)[3H]epibatidine to nicotinic receptors in rat brain. In rat forebrain homogenates, (+/-)(-)[3H]epibatidine binds to two sites, with apparent affinities of 15 pM and 360 pM. Both of these binding sites have pharmacological profiles consistent with neuronal nicotinic receptors and a similar brain regional distribution. (+/-)(-)[3H]Epibatidine also binds to sites in rat adrenal gland, suggesting that it can label a subtype of nicotinic receptor found in peripheral ganglia as well as the subtype that predominates in brain. In human cerebral cortex as well, (+/-)(-)[3H]epibatidine binds two sites, one of which appears to have an affinity of < 1 pM. We conclude that (+/-)(-)[3H]epibatidine should be a very useful new tool for characterizing the properties and regulation of neuronal nicotinic receptors, including those not easily measurable with other radioligands.
表蛙毒素是一种生物碱，最初由戴利等人从厄瓜多尔三色箭毒蛙的皮肤中分离出来[《美国化学会志》102:803 - 836(1980)]，发现它对神经元烟碱受体具有非常高的亲和力，并在该受体上作为强效激动剂发挥作用。在此，我们测定并表征了(±)( - )[³H]表蛙毒素与大鼠脑内烟碱受体的结合情况。在大鼠前脑匀浆中，(±)( - )[³H]表蛙毒素与两个位点结合，表观亲和力分别为15 pM和360 pM。这两个结合位点的药理学特征均与神经元烟碱受体一致，且脑区分布相似。(±)( - )[³H]表蛙毒素也与大鼠肾上腺中的位点结合，这表明它能够标记在外周神经节中发现的烟碱受体亚型以及在脑中占主导地位的亚型。在人类大脑皮层中，(±)( - )[³H]表蛙毒素同样与两个位点结合，其中一个位点的亲和力似乎小于1 pM。我们得出结论，(±)( - )[³H]表蛙毒素应该是一种非常有用的新型工具，可用于表征神经元烟碱受体的特性和调节，包括那些难以用其他放射性配体测量的受体。
