Subhash M N, Srinivas B N, Vinod K Y, Jagadeesh S
Department of Neurochemistry, National Institute of Mental Health and Neurosciences, Bangalore, India.
Neurochem Res. 1998 Oct;23(10):1321-6. doi: 10.1023/a:1020756519425.
Inactivation of 5-HT1A and [3H]5-HT binding sites by N-Ethoxycarbonyl-2-ethoxy-1, 2-dihydroquinoline (EEDQ) was studied in regions of rat brain. After exposure to EEDQ (4 mg/kg body wt.) for 7 days, it is observed that the density of 5-HT1 receptor sites was decreased by nearly 20% in both cortex and hippocampus. The decrease, however, in 5-HT1A sites was more significant (70%) in both the regions. The affinity of [3H]5-HT to 5-HT1 sites was decreased significantly in both cortex and hippocampus after exposure to EEDQ, without affecting the Kd of 5-HT1A sites. Displacement studies suggested that EEDQ has high affinity to 5-HT1 sites with a Ki of 42.9+/-2.4 nM. After exposure neither basal nor 5-HT stimulated adenylyl cyclase activity was changed in cortex. The results of this study suggest that EEDQ decreases the density of 5-HT1 and 5-HT1A receptor sites but does not cause functional downregulation of these sites in rat brain.
在大鼠脑区研究了N-乙氧羰基-2-乙氧基-1,2-二氢喹啉（EEDQ）对5-HT1A和[3H]5-HT结合位点的失活作用。在给予EEDQ（4mg/kg体重）7天后，观察到皮质和海马中5-HT1受体位点的密度均降低了近20%。然而，这两个区域中5-HT1A位点的降低更为显著（70%）。暴露于EEDQ后，皮质和海马中[3H]5-HT与5-HT1位点的亲和力均显著降低，但不影响5-HT1A位点的解离常数（Kd）。置换研究表明，EEDQ对5-HT1位点具有高亲和力，其抑制常数（Ki）为42.9±2.4nM。暴露后，皮质中基础及5-HT刺激的腺苷酸环化酶活性均未改变。本研究结果表明，EEDQ可降低大鼠脑中5-HT1和5-HT1A受体位点的密度，但不会导致这些位点的功能下调。
