Perry D C, Kellar K J
Department of Pharmacology, George Washington University Medical Center, Washington, DC, USA.
J Pharmacol Exp Ther. 1995 Nov;275(2):1030-4.
Epibatidine, a frog skin alkaloid, is a nicotinic receptor agonist with potent analgesic activity. We used in vitro receptor autoradiographic techniques to map binding sites for [3H]epibatidine in rat brain, and those for another nicotinic agonist, [3H]cytisine. Both [3H]epibatidine and [3H]cytisine are excellent radioligands for autoradiography. [3H]Epibatidine in particular binds with very high affinity and extremely low nonspecific binding. In the present study, the distribution of binding was almost identical for both radioligands and closely resembled that of previously published autoradiographic studies with two other nicotinic ligands, [3H]acetylcholine and [3H]nicotine. Brain regions demonstrating the highest levels of [3H]epibatidine binding included the interpeduncular nucleus, medial habenular nucleus, fasciculus retroflexus, superficial gray layer of the superior colliculus and numerous thalamic nuclei, including the anteroventral, dorsal lateral geniculate and gelatinosus nuclei. Quantitative analysis revealed that [3H]epibatidine binding was greater than [3H]cytisine binding in several regions. In particular, [3H]epibatidine clearly labeled the optic nerve, optic chiasm and optic tract, whereas [3H]cytisine binding to these structures did not exceed background levels. Other regions in which [3H]epibatidine binding was greater than that of [3H]cytisine included the medial habenula, fasciculus retroflexus, olivary pretectal nucleus and superficial gray layer of the superior colliculus. The differences in labeling between these two nicotinic ligands may arise from receptor heterogeneity in brain nicotinic receptors and the ability of [3H]epibatidine to label more than one subtype of nicotine receptor.
埃皮巴蒂啶是一种蛙皮生物碱，是一种具有强效镇痛活性的烟碱受体激动剂。我们使用体外受体放射自显影技术来绘制大鼠脑中[3H]埃皮巴蒂啶以及另一种烟碱激动剂[3H]金雀花碱的结合位点图谱。[3H]埃皮巴蒂啶和[3H]金雀花碱都是用于放射自显影的优良放射性配体。特别是[3H]埃皮巴蒂啶以非常高的亲和力和极低的非特异性结合进行结合。在本研究中，两种放射性配体的结合分布几乎相同，并且与先前发表的使用另外两种烟碱配体[3H]乙酰胆碱和[3H]尼古丁的放射自显影研究结果非常相似。显示[3H]埃皮巴蒂啶结合水平最高的脑区包括脚间核、内侧缰核、后屈束、上丘浅灰层以及众多丘脑核，包括腹前核、背外侧膝状体核和胶状核。定量分析显示，在几个区域中[3H]埃皮巴蒂啶的结合大于[3H]金雀花碱的结合。特别是，[3H]埃皮巴蒂啶清晰地标示出视神经、视交叉和视束，而[3H]金雀花碱与这些结构的结合不超过背景水平。[3H]埃皮巴蒂啶结合大于[3H]金雀花碱结合的其他区域包括内侧缰核、后屈束、橄榄顶盖前核和上丘浅灰层。这两种烟碱配体在标记上的差异可能源于脑烟碱受体的受体异质性以及[3H]埃皮巴蒂啶标记不止一种烟碱受体亚型的能力。
