Genomic responses to 5-HT1A or 5-HT2A/2C receptor activation is differentially regulated in four regions of rat brain.
Genomic responses to 5-HT1A or 5-HT2A/2C receptor activation is differentially regulated in four regions of rat brain.
复制标题
对 5-HT1A 或 5-HT2A/2C 受体激活的基因组反应在大鼠大脑的四个区域中受到差异性调节。
DOI：
10.1016/0014-2999(96)00233-6
复制
发表时间：
1996
影响因子：
5
通讯作者：
Friedman,E
中科院分区：
文献类型：
--
作者：
Tilakaratne,N;Friedman,E
用8-OH-DPAT(8-羟基-2-(二正丙氨基)四氢呋喃)或DOI(1-(2，5-dimethoxy-4-iodophenyl)-2-aminopropane).激活受体后，通过定量测定即刻早期基因c-fos、ngflc和Tisl的变化，来评估大脑5-HT1a和5-HT2Ac受体的功能刺激任何一类5-羟色胺受体都能不同程度地诱导大脑皮层、海马区和小脑的三个即刻早期基因的表达，但对纹状体没有影响。对8-OH-DPAT的反应早于DOI。Way 100135(N-tertiobutyl-3-[4-(2-methoxyphenyl)-piperazinyl]-2-phenylpropanamide)，是5-HTIA受体拮抗剂，可阻断8-OH-DPAT效应，但不能阻断对DOI的反应。途径100135本身也引起了相对较小的基因组反应。酮色林可完全消除DOI诱导的基因组反应。这一结果支持了早期的发现，即5-HT1A受体在额叶皮质和海马区分布丰富。此外，对8-OH-DPAT的强劲基因组反应以及与小脑中5-HT1AmRNA的cDNA探针的Northern杂交清楚地表明5-HT1A受体在该脑区的功能表达。对5-HT2受体激动剂的反应，DOI支持皮质中这些受体的更丰富，而在海马区和小脑中的水平相对较低。结果表明，三个即刻早期基因之间的诱导模式取决于大脑区域和所涉及的5-羟色胺受体亚型。
The functional profiles of brain 5-HT1Aand 5-HT2A creceptors were assessed by quantitating changes in the immediate early genes — c-fos, ngflc and tisl, following receptor activation with either 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) or DOI (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane). Stimulation of either class of 5-HT receptor elicited an induction of all three immediate early genes to varying extents in cortex, hippocampus and cerebellum, but not in striatum. The responses to 8-OH-DPAT peaked earlier than those to DOI. WAY 100135 (N-tertiobutyl-3-[4-(2-methoxyphenyl)-piperazinyl]-2-phenylpropanamide), the putative 5-HT1Areceptor antagonist blocked the 8-OH-DPAT effect but not the responses to DOI. WAY 100135 by itself also elicited a relatively smaller genomic response. Ketanserin completely abolished the DOI-induced genomic responses. The results support the earlier findings that 5-HT1Areceptor sites are abundant in frontal cortex and hippocampus. In addition, the robust genomic responses to 8-OH-DPAT as well as Northern hybridization with a cDNA probe for 5-HT1AmRNA in the cerebellum clearly implicate the functional expression of 5-HT1Areceptors in this brain region. The responses to the 5-HT2receptor agonist, DOI support a greater abundance of these receptors in the cortex, and relatively lower levels in hippocampus and cerebellum. The results suggest a differential induction pattern among the three immediate-early genes depending on the brain region and the 5-HT receptor subtype involved.