Jakeman L B, To Z P, Eglen R M, Wong E H, Bonhaus D W
Department of Neurosciences, Institute of Pharmacology, Palo Alto, CA 94303.
Neuropharmacology. 1994 Aug;33(8):1027-38. doi: 10.1016/0028-3908(94)90162-7.
Recent radioligand binding studies have demonstrated the presence of 5-HT4 receptors throughout the nigrostriatal and mesolimbic systems of mammalian brain. In many regions, the binding has not yet been correlated with functional responses. The present study was carried out to fully characterize the regional distribution of 5-HT4 receptors in brain sections from three species using two structurally distinct radioligands, [3H]GR113808, and [3H]BIMU-1. The highest density of 5-HT4 receptors labeled with [3H]GR113808 was found in the olfactory tubercle, substantia nigra, ventral pallium and striatum of rat and guinea pig, and similar regions of pig-tail macaque monkey. A similar distribution of 5-HT4 receptors was observed in guinea pig brain using [3H]BIMU-1. With either ligand, the binding was saturable and of high affinity (Kd = 0.08-0.53 nM for [3H]GR113808; 1.4-3.0 nM for [3H]BIMU-1). These results extend previous distribution studies, confirm the heterogenous distribution of 5-HT4 receptors throughout the nigrostriatal and mesolimbic systems of three species, and demonstrate a similar distribution using two structurally distinct 5-HT4 radioligands.
最近的放射性配体结合研究表明，5-羟色胺4（5-HT4）受体存在于哺乳动物脑的黑质纹状体和中脑边缘系统中。在许多区域，这种结合尚未与功能反应相关联。本研究旨在使用两种结构不同的放射性配体[3H]GR113808和[3H]BIMU-1，全面表征三种物种脑切片中5-HT4受体的区域分布。用[3H]GR113808标记的5-HT4受体最高密度出现在大鼠、豚鼠的嗅结节、黑质、腹侧皮层和纹状体，以及猪尾猕猴的类似区域。使用[3H]BIMU-1在豚鼠脑中观察到5-HT4受体的类似分布。使用任何一种配体，结合都是可饱和的且具有高亲和力（[3H]GR113808的Kd = 0.08 - 0.53 nM；[3H]BIMU-1的Kd = 1.4 - 3.0 nM）。这些结果扩展了先前的分布研究，证实了5-HT4受体在三种物种的黑质纹状体和中脑边缘系统中的异质分布，并证明了使用两种结构不同的5-HT4放射性配体的类似分布。
