Guinea pig hippocampal 5-HT(1E) receptors: a tool for selective drug development.
Guinea pig hippocampal 5-HT(1E) receptors: a tool for selective drug development.
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DOI：
10.1111/j.1471-4159.2009.05958.x
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发表时间：
2009-04
影响因子：
4.7
通讯作者：
Teitler M
中科院分区：
文献类型：
--
作者：
Klein MT;Teitler M
最近的研究表明，最初在人脑组织中发现的5-羟色胺（5-HT） 1E受体在大鼠或小鼠大脑中不表达。因此，关于5-HT1E受体药物开发的报道很少。然而，5-HT1E受体mRNA在豚鼠大脑中有表达。为了将该物种作为5-HT1E药物开发的动物模型，我们确定了表现出5-羧基氨基色胺（5-CT）、利坦色林和LY344864 -不敏感[3H]5-HT结合（5-HT1E受体的特征）的大脑区域。在5-HT1E受体密度足够高的海马匀浆液中，使用100nM 5-CT、30nM利坦色林和100nM LY344864来掩盖[3H]5-HT与非5-HT1E受体的结合。[3H]5-HT的Kd值为5.7±0.7nM，与克隆受体的Kd值为6.5±0.6nM无法区分。16种药物对克隆豚鼠5-HT1E受体和海马表达豚鼠5-HT1E受体的亲和力基本相同（R2=0.97）。这些发现表明，在这些条件下，研究豚鼠脑内5-HT1E受体的放射自显影分布和信号转导是可行的。使用豚鼠作为动物模型，将为该受体的可能功能和选择性人类5-HT1E药物的治疗潜力提供重要的见解。
Recent studies have indicated that the serotonin (5-HT) 1E receptor, originally discovered in human brain tissue, is not expressed in rat or mouse brain. Thus there have been few reports on 5-HT1E receptor drug development. However, expression of 5-HT1E receptor mRNA has been shown in guinea pig brain. To establish this species as an animal model for 5-HT1E drug development, we identified brain regions that exhibit 5-carboxyamidotryptamine (5-CT), ritanserin, and LY344864 –insensitive [3H]5-HT binding (characteristic of the 5-HT1E receptor). In hippocampal homogenates, where 5-HT1E receptor density was sufficiently high for radioligand binding analysis, 100nM 5-CT, 30nM ritanserin, and 100nM LY344864 were used to mask [3H]5-HT binding at non-5-HT1E receptors. The Kd of [3H]5-HT was 5.7±0.7nM and is indistinguishable from the cloned receptor Kd of 6.5±0.6nM. The affinities of 16 drugs for the cloned and hippocampal-expressed guinea pig 5-HT1E receptors are essentially identical (R2=0.97). These findings indicate that using these conditions autoradiographical distribution and signal transduction studies of the 5-HT1E receptor in guinea pig brain are feasible. Using the guinea pig as an animal model should provide important insights into possible functions of this receptor and the therapeutic potential of selective human 5-HT1E drugs.
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DOI：
10.3109/10401239409148985
发表时间：
1994-06-01
期刊：
Annals of clinical psychiatry : official journal of the American Academy of Clinical Psychiatrists
影响因子：
--
作者：
Roth, B L
通讯作者：
Roth, B L
影响因子：
5
作者：
LOWTHER, S;DEPAERMENTIER, F;HORTON, RW
通讯作者：
HORTON, RW
影响因子：
4.7
作者：
Adham, N;Bard, JA;Branchek, TA
通讯作者：
Branchek, TA
影响因子：
5
作者：
Bai, F;Yin, TG;Nelson, DL
通讯作者：
Nelson, DL
影响因子：
6.1
作者：
GLENNON, RA;TITELER, M;MCKENNEY, JD
通讯作者：
MCKENNEY, JD