Bertelsen G A, Rebello S, Gulati A
Department of Pharmacodynamics, University of Illinois, Chicago 60612.
Neurobiol Aging. 1992 Jul-Aug;13(4):513-9. doi: 10.1016/0197-4580(92)90080-h.
Characteristics of endothelin receptors were studied in male Fischer 344 rats at 4-, 15- and 24-months of age and [125I]ET-1 binding showed a single high affinity binding site in their cerebral cortex and spinal cord membranes. The density and affinity of ET binding sites were found to be similar in rats of various age groups. To determine the affinity of ET isotypes to ET-1 binding sites in cerebral cortex and spinal cord, competition studies were performed and K(i) values of ET-1, ET-2 and ET-3 for [125I] ET-1 binding sites were determined. It was found that ET-1 had 100 and ET-2 had 25-100 times lower K(i) values as compared to ET-3, indicating that ET receptors in cerebral cortex and spinal cord are of ETA type. In spinal cord, the K(i) values of ET-1 and ET-2 for ET receptor were found to be similar. However, in cerebral cortex the K(i) values of ET-1 were found to be at least 6 times lower than ET-2. It is inferred that there are two subtypes of ET(A) receptors, ET(A1) which have higher affinity for ET-1 in comparison to ET-2, as found in cerebral cortex and ET(A2) which have higher affinity for ET-2, as found in spinal cord. The K(i) and IC50 values of ET-1, ET-2, and ET-3 for [125I]ET-1 binding sites in cerebral cortex and spinal cord were found to be similar in 4-, 15- and 24-month-old rats.(ABSTRACT TRUNCATED AT 250 WORDS)
在4月龄、15月龄和24月龄的雄性Fischer 344大鼠中研究了内皮素受体的特性，[125I]ET-1结合在其大脑皮层和脊髓膜中显示出单一的高亲和力结合位点。发现不同年龄组大鼠中ET结合位点的密度和亲和力相似。为了确定内皮素同型物对大脑皮层和脊髓中ET-1结合位点的亲和力，进行了竞争研究，并测定了ET-1、ET-2和ET-3对[125I]ET-1结合位点的K(i)值。发现与ET-3相比，ET-1的K(i)值低100倍，ET-2的K(i)值低25-100倍，表明大脑皮层和脊髓中的ET受体为ETA型。在脊髓中，发现ET-1和ET-2对ET受体的K(i)值相似。然而，在大脑皮层中，发现ET-1的K(i)值比ET-2至少低6倍。据推测，ET(A)受体有两种亚型，如在大脑皮层中发现的对ET-1亲和力高于ET-2的ET(A1)，以及如在脊髓中发现的对ET-2亲和力更高的ET(A2)。在4月龄、15月龄和24月龄大鼠中，发现ET-1、ET-2和ET-3对大脑皮层和脊髓中[125I]ET-1结合位点的K(i)和IC50值相似。（摘要截短于250字）
