5HT1B Receptor Agonists Inhibit Light-Induced Phase Shifts of Behavioral Circadian Rhythms and Expression of the Immediate–Early Gene c-fos in the Suprachiasmatic Nucleus
5HT1B Receptor Agonists Inhibit Light-Induced Phase Shifts of Behavioral Circadian Rhythms and Expression of the Immediate–Early Gene c-fos in the Suprachiasmatic Nucleus
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5HT1B 受体激动剂抑制光诱导的行为昼夜节律相移和视交叉上核中立即早期基因 c-fos 的表达
作者：
G. E. Pickard;E. Weber;P. A. Scott;Anne F. Riberdy;M. A. Rea
视交叉上核（SCN）是一个昼夜节律振荡器，是哺乳动物昼夜节律系统的重要组成部分。它接受来自视网膜和中脑缝的传入。视网膜传入介导SCN的光夹带，而源自中脑的5-羟色胺能传入调节SCN中的光反应;然而，SCN中负责这些调节作用的5-羟色胺（5 HT）受体亚型尚未得到很好的表征。在这项研究中，我们测试的假设，即5 HT 1B受体位于突触前视网膜轴突终端在SCN和这些受体的激活抑制视网膜输入。5-HT 1B受体激动剂TFMPP和CGS 12066 A，全身给药，抑制光诱导的相位偏移的昼夜活动节律在相位延迟和相位提前时间点以剂量依赖性的方式。这种抑制作用不受先前全身应用的选择性5 HT 1A受体拮抗剂（+）WAY 100135或5 HT 2受体拮抗剂美舒麦角碱的影响，而预处理与非选择性5 HT 1拮抗剂甲硫氨酸显着减弱TFMPP的效果。TFMPP也产生了剂量依赖性的减少光刺激Fos的表达在SCN，虽然在尾侧SCN的背外侧方面的一小部分细胞是TFMPP不敏感的。将TFMPP（1 mm）注入SCN，可完全抑制光诱导的相位提前。最后，双侧眼眶摘除术降低了SCN 5 HT 1B受体的密度，这是使用[125 I]-iodocyanopindolol确定5 HT 1B结合位点确定的。这些结果是一致的解释，5 HT 1B受体位于突触前视网膜末梢的SCN和激活这些受体的5 HT 1B激动剂抑制retinohypothalamic输入。
The suprachiasmatic nucleus (SCN) is a circadian oscillator and a critical component of the mammalian circadian system. It receives afferents from the retina and the mesencephalic raphe. Retinal afferents mediate photic entrainment of the SCN, whereas the serotonergic afferents originating from the midbrain modulate photic responses in the SCN; however, the serotonin (5HT) receptor subtypes in the SCN responsible for these modulatory effects are not well characterized. In this study, we tested the hypothesis that 5HT1B receptors are located presynaptically on retinal axon terminals in the SCN and that activation of these receptors inhibits retinal input. The 5HT1B receptor agonists TFMPP and CGS 12066A, administered systemically, inhibited light-induced phase shifts of the circadian activity rhythm in a dose-dependent manner at phase delay and phase advance time points. This inhibition was not affected by previous systemic application of either the selective 5HT1A receptor antagonist (+)WAY 100135 or by the 5HT2 receptor antagonist mesulergine, whereas pretreatment with the nonselective 5HT1 antagonist methiothepin significantly attenuated the effect of TFMPP. TFMPP also produced a dose-dependent reduction in light-stimulated Fos expression in the SCN, although a small subset of cells in the dorsolateral aspect of the caudal SCN were TFMPP-insensitive. TFMPP (1 mm) infused into the SCN produced complete inhibition of light-induced phase advances. Finally, bilateral orbital enucleation reduced the density of SCN 5HT1B receptors as determined using [125I]-iodocyanopindolol to define 5HT1Bbinding sites. These results are consistent with the interpretation that 5HT1B receptors are localized presynaptically on retinal terminals in the SCN and that activation of these receptors by 5HT1B agonists inhibits retinohypothalamic input.
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DOI：
--
发表时间：
1989-04
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
I. Lucki;H. R. Ward;A. Frazer
通讯作者：
I. Lucki;H. R. Ward;A. Frazer
金鱼视网膜中乙酰胆碱受体的合成和视顶盖的转运。
DOI：
10.1126/science.3715468
发表时间：
1986
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Henley,JM;Lindstrom,JM;Oswald,RE
通讯作者：
Oswald,RE
人类 5-羟色胺 1B 受体的表征。
DOI：
--
发表时间：
1992
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Jin,H;Oksenberg,D;Ashkenazi,A;Peroutka,SJ;Duncan,AM;Rozmahel,R;Yang,Y;Mengod,G;Palacios,JM;O'Dowd,BF
通讯作者：
O'Dowd,BF
应用[125I]碘氰吲哚洛尔测定大鼠脑内5-羟色胺1B受体。
DOI：
--
发表时间：
1988
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Offord,SJ;Ordway,GA;Frazer,A
通讯作者：
Frazer,A
成年仓鼠上丘突触前 5-HT1B 受体对视网膜顶盖传输的调节。
影响因子：
2.5
作者：
Mooney,RD;Shi,MY;Rhoades,RW
通讯作者：
Rhoades,RW