Expression and fine mapping of murine vasoactive intestinal peptide receptor 1
Expression and fine mapping of murine vasoactive intestinal peptide receptor 1
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DOI：
10.1385/jmn:17:3:311
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发表时间：
2001-12-01
影响因子：
3.1
通讯作者：
Krahe, R
中科院分区：
文献类型：
--
作者：
Karacay, B;O'Dorisio, MS;Krahe, R
血管活性肠肽（VIP）作为神经递质、激素和细胞因子在神经、内分泌和免疫系统中发挥着多种作用。VIP广泛分布于中枢和外周神经系统（CNS/PNS）的神经元中，最近发现其是重要的神经保护剂。VIP的作用是通过特异性G蛋白偶联受体介导的。我们克隆了VIP受体亚型1（VIPR 1（dagger）或VPAC（1））的cDNA，并在小鼠中展示了定量表达谱。荧光实时逆转录-聚合酶链反应（RT-PCR）分析表明，VPAC（1）在所有检查的组织中表达。在小肠和结肠中表达最高，其次是肝脏和脑。VPAC（1）在前脑和小脑的高水平表达表明，VPAC（1）可能介导VIP的神经保护作用。我们已经完善了小鼠、大鼠和人类VPAC（1）基因的染色体定位。VPAC（1）基因的精细定位延伸了小鼠9号染色体、大鼠8 q32和人3p21.33-p21.31的远端区域之间的相应同线性区域。因此，VPAC（1）构成了定位于人3 p22-p21的肿瘤抑制功能的功能位置候选者，在小细胞肺癌（SCLC）细胞系和原发性肿瘤中观察到杂合性丢失。小鼠VPAC（1）cDNA序列的可用性将促进VPAC（1）无效突变动物的产生。这些研究将最终增强我们对VIP在神经系统中作用的理解。
Vasoactive intestinal peptide (VIP) plays multiple roles in the nervous, endocrine, and immune systems as a neurotransmitter, a hormone, and a cytokine. VIP is widely distributed in neurons of the central and peripheral nervous systems (CNS/PNS), and recently has been found to be an important neuroprotective agent. VIP actions are mediated through specific G protein-coupled receptors. We have cloned the cDNA of VIP receptor subtype 1 (VIPR1(dagger) or VPAC(1) and have demonstrated the quantitative expression profile in mice. Fluorometric real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis demonstrated that VPAC(1) is expressed in all tissues examined. Expression was highest in the small intestine and colon followed by the liver and brain. The high level of VPAC(1) expression in forebrain and cerebellum suggests that VPAC(1) may mediate the neuroprotective effect of VIP. We have refined the chromosomal localization of the mouse, rat, and human VPAC(1) genes. This fine mapping of the VPAC(1) gene extends the respective regions of synteny between the distal region of mouse chromosome 9, rat chromosome 8q32, and human chromosome 3p2l.33-p21.31. Thus, VPAC(1) constitutes a functional-positional candidate for the tumor-suppressor function mapped to human 3p22-p21 where loss-of-heterozygosity is observed in small-cell lung carcinoma (SCLC) cell lines and primary tumors. Availability of the cDNA sequences for mouse VPAC(1) will facilitate the generation of VPAC(1) null mutant animals. Such studies will ultimately enhance our understanding of the role of VIP in the nervous system.