Antagonism of NPY-induced feeding by pretreatment with cyclic AMP response element binding protein antisense oligonucleotide
Antagonism of NPY-induced feeding by pretreatment with cyclic AMP response element binding protein antisense oligonucleotide
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DOI：
10.1054/npep.2000.0807
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发表时间：
2000-06-01
期刊：
影响因子：
2.9
通讯作者：
Balasubramaniam, A
中科院分区：
文献类型：
--
作者：
Chance, WT;Sheriff, S;Balasubramaniam, A
虽然第二信使系统subserving神经肽Y（NPY）介导的行为已被确定为多种受体在几个组织中，下游的信号事件是不为人所知。核结合蛋白，环磷酸腺苷反应元件结合蛋白（CREB）似乎是一个转录因子，被激活后，注射到大鼠下丘脑神经肽Y。为了确定CREB介导NPY诱导进食的功能性质，将注射插管植入18只大鼠的穹窿周围下丘脑。用CREB反义寡核苷酸（15 μ g）治疗7只大鼠在治疗后长达一周显著拮抗NPY进食，而CREB正义寡核苷酸（15 μ g）的类似注射对NPY诱导的进食没有显著影响。反义寡核苷酸治疗后两周，通过注射NPY再次引起进食。CREB反义寡核苷酸处理后两天下丘脑CREB蛋白也显著降低。这些结果表明，CREB的激活，可能通过磷酸化，可能是一个必要的事件的信号转导的神经肽Y刺激到摄食行为。(C)2000年哈考特出版社有限公司
Although second messenger systems subserving neuropeptide Y (NPY)-mediated behaviors have been identified for a variety of receptors in several tissues, downstream signaling events are not well known. The nuclear binding protein, cyclic AMP response element binding protein (CREB) appears to be a transcription factor that is activated following injection of NPY into rat hypothalamus. To allow determination of the functional nature of CREB mediation of NPY-induced feeding, injection cannulae were implanted into the perifornical hypothalamus of 18 rats. Treatment of seven rats with CREB antisense oligonucleotide (15 ug) significantly antagonized NPY feeding for up to one week after treatment, while similar injections of CREB sense oligonucleotide (15 ug) had no significant effect on NPY-induced feeding. Two weeks after the antisense oligonucleotide treatment, feeding was once again elicited by the injection of NPY. Hypothalamic CREB protein was also reduced significantly two days after the CREB antisense oligonucleotide treatment. These results suggest that activation of CREB, probably through phosphorylation, may be a necessary event for the signal transduction of NPY stimulation into feeding behavior. (C) 2000 Harcourt Publishers Ltd.