大鼠脊髓中一种新型5-羟色胺（5-HT）结合位点的鉴定。

Identification of a novel 5-HT(1) binding site in rat spinal cord.

作者信息

Zemlan F P, Schwab E F, Maureen Murphy R, Behbehani M M

机构信息

Alzheimer's Research Center, Department of Psychiatry, University of Cincinnati College of Medicine, 231 Bethesda Avenue, Cincinnati, OH 45267-0559, USA; Department of Physiology and Biophysics, University of Cincinnati College of Medicine, 231 Bethesda Avenue, Cincinnati, OH 45267-0559, U.S.A.

出版信息

Neurochem Int. 1990;16(4):507-13. doi: 10.1016/0197-0186(90)90010-q.

DOI:10.1016/0197-0186(90)90010-q

PMID:20504589

Abstract

High affinity, specific [(3)H]5-hydroxytryptamine (5-HT) binding to spinal cord synaptosomes was examined to identify the 5-HT receptor subtypes present. Computer nonlinear regression analysis of competition studies employing 8-OH-DPAT indicated that this 5-HT(1A) selective agonist demonstrated high affinity competition (K(i = 1.3 nM)) for 24.6 +/- 0.7% of the total [(3)H]5-HT binding sites. Competition studies employing the 5-HT(1B) selective agonist RU24969, in the presence of 100 nM 8-OH-DPAT, indicated that RU24969 demonstrated high affinity (K(i = 1.1 nM)) competitive inhibition for 26.2 +/- 1.4% of all [(3)H]5-HT binding sites. Neither 5-HT(1C), 5-HT(1D), 5-HT(2) nor 5-HT(3) selective compounds demonstrated any high affinity competition for the residual 49% of specific [(3)H]5-HT binding. Therefore, three major classes of [(3)H]5-HT binding sites could be demonstrated in spinal cord synaptosomes: 5-HT(1A), 5-HT(1B) and a novel [(3)H]5-HT binding site which respectively represented 25, 26 and 49% of spinal cord synaptosomal [(3)H]5-HT binding. Further studies focusing on the function of the latter binding site are needed to determine if the presently identified novel binding site is the major 5-HT(1) receptor subtype present in spinal cord.

摘要

研究了高亲和力、特异性的[(3)H]5-羟色胺（5-HT）与脊髓突触体的结合情况，以确定存在的5-HT受体亚型。使用8-OH-DPAT进行竞争研究的计算机非线性回归分析表明，这种5-HT(1A)选择性激动剂对24.6±0.7%的总[(3)H]5-HT结合位点表现出高亲和力竞争（K(i = 1.3 nM)）。在100 nM 8-OH-DPAT存在的情况下，使用5-HT(1B)选择性激动剂RU24969进行的竞争研究表明，RU24969对所有[(3)H]5-HT结合位点的26.2±1.4%表现出高亲和力（K(i = 1.1 nM)）竞争性抑制。5-HT(1C)、5-HT(1D)、5-HT(2)或5-HT(3)选择性化合物对剩余49%的特异性[(3)H]5-HT结合均未表现出任何高亲和力竞争。因此，在脊髓突触体中可证明存在三类主要的[(3)H]5-HT结合位点：5-HT(1A)、5-HT(1B)和一个新的[(3)H]5-HT结合位点，它们分别占脊髓突触体[(3)H]5-HT结合的25%、26%和49%。需要进一步针对后一种结合位点的功能进行研究，以确定目前鉴定出的新结合位点是否是脊髓中存在的主要5-HT(1)受体亚型。