PILOT STUDY--PROLACTIN RELEASING PEPTIDE AND NICOTINE
PILOT STUDY--PROLACTIN RELEASING PEPTIDE AND NICOTINE
批准号:
6660947
负责人:
OLIVIER CIVELLI
金额:
$17.92万
依托单位国家:
美国
项目类别:
财政年份:
2002
资助国家:
美国
项目状态:
已结题
起止时间:
2002-09-15 至 2003-08-31
中文摘要
催乳素(PRL)的分泌不仅支持生殖功能和泌乳,而且在压力下维持稳态功能。因此,已知PRL释放不仅受内源性释放因子调节,而且受具有抗应激活性的外源性化学物质调节。其中突出的是尼古丁,其通过作用CNS位点,特别是孤束核(NTS)引起PRL的释放。尼古丁调节PRL释放的机制知之甚少。最近,一个3 I-氨基酸肽,命名为催乳素释放肽(PrRP),被分离出来,有效地诱导催乳素释放从初级垂体细胞。我们的初步数据表明,PrRP mRNA存在于NTS,而其受体被发现在下丘脑。这些数据表明,PrRP可能是尼古丁诱导的PRL释放的另一个重要介质。尼古丁刺激后,PrRP可从NTS释放,作用于下丘脑并诱导其他催乳素释放肽的释放,或通过在门静脉血中分泌并直接作用于垂体。因此,我们建议通过显示PrRP存在于尼古丁敏感(~阳性)NTS神经元中以及尼古丁诱导PrRP在脑脊液中释放来检验PrRP与尼古丁之间直接联系的假设。
英文摘要
Prolactin (PRL) is secreted not only to support reproductive functions and lactation but also to maintain homeostatic functions under stress. Consequently, PRL release is known to be regulated not only by endogenous releasing factors but also by exogenous chemical substances with anti-stress activities. Prominent among these is nicotine which causes the release of PRL by acting CNS sites, in particular the nucleus tractus solitarius (NTS). The mechanism by which nicotine modulates PRL release is poorly understood. Recently, a 3 I-amino acid peptide, named the Prolactin Releasing Peptide (PrRP), was isolated which potently induced prolactin release from primary pituitary cells. Our preliminary data indicate that the PrRP mRNA is present in the NTS while its receptor is found in the hypothalamus. These data suggest that PrRP may be another important mediator of nicotine-induced PRL release. Upon nicotine stimulation, PrRP may be released from the NTS to act either on the hypothalamus and induce the release of other prolactin-releasing peptides or by being secreted in the potal blood and acting directly on the pituitary. We therefore propose to test the hypothesis of a direct link between PrRP and nicotine, by showing that PrRP is present in the nicotine sensitive (~ positive) NTS neurons and that nicotine induces PrRP release in the cerebrospinal fluid.
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会议论文
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海外基金