Characterization of melatonin-induced fos-like immunoreactivity in the hypothalamic suprachiasmatic nucleus of the rat

被引:3
作者
Mullins, UL
Gianutsos, G
Eison, AS
机构
[1] Bristol Myers Squibb Co, Neurosci Drug Discovery, Dept 408, Wallingford, CT 06492 USA
[2] Univ Connecticut, Dept Pharmaceut Sci, Storrs, CT 06269 USA
来源
JOURNAL OF RECEPTOR AND SIGNAL TRANSDUCTION RESEARCH | 1999年 / 19卷 / 05期
关键词
D O I
10.3109/10799899909042873
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The hypothalamic suprachiasmatic nucleus (SCN) is primarily responsible for the regulation of circadian rhythmicity. Melatonin, the pineal-derived neurohormone, modulates the rhythmic output of the SCN. Properly timed exposure to melatonin is able to induce changes in rhythmic function and thereby entrain circadian rhythms of activity. c-fos is an immediate early gene that is transiently expressed in neurons in response to receptor activation. The ventrolateral portion of the SCN (vSCN) is activated in response to phase-shifting stimuli, an event which is marked by an increase in the expression of c-fos. In the present study, rats systemically administered the melatonin agonist 2-iodomelatonin at CT 22 demonstrated significant dose-dependent Fos immunoreactivity within the vSCN, an effect which was significantly inhibited by the melatonin antagonist N-acetyltryptamine. The Fos expression observed in the vSCN was not affected by treatment with the serotonin antagonist ketanserin or the alpha-adrenergic antagonist phentolamine. Moreover, antisense oligonucleotides to c-fos, significantly blocked the ability of 2-iodomelatonin to induce Fos expression in the vSCN at CT 22. These results pharmacologically characterize melatonin-induced c-fos expression in the rat vSCN and provide evidence to support a c-fos-mediated mechanism through which the activation of melatonin receptors may be linked to the long-term molecular regulation of circadian rhythms controlled by the SCN.
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页码:781 / 801
页数:21
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