EXTRAPITUITARY EXPRESSION OF THE RAT V1B VASOPRESSIN RECEPTOR GENE
EXTRAPITUITARY EXPRESSION OF THE RAT V1B VASOPRESSIN RECEPTOR GENE
复制标题
DOI：
10.1073/pnas.92.15.6783
复制
发表时间：
1995-07-18
影响因子：
11.1
通讯作者：
BROWNSTEIN, MJ
中科院分区：
文献类型：
--
作者：
LOLAIT, SJ;OCARROLL, AM;BROWNSTEIN, MJ
[Arg（8）]加压素（AVP）通过作用于V1 b AVP受体刺激促肾上腺皮质激素从垂体前叶释放。该受体可通过其对AVP结构类似物的不同结合亲和力与血管/肝V1 a和肾V2 AVP受体区分开。最近的研究表明，克隆的V1和V2受体在结构上是相关的。我们已经分离出一个克隆编码的V1 b受体从大鼠垂体cDNA文库使用聚合酶链反应（PCR）为基础的方法。大鼠Vlb受体是421个氨基酸的蛋白质，与Vla和V2受体具有37-50%的同一性。这些鸟嘌呤核苷酸结合蛋白偶联受体的七个假定的跨膜结构域的同源性特别高。重组受体在哺乳动物细胞中的表达显示出与大鼠垂体V1 b受体相同的AVP激动剂和拮抗剂的结合特异性。在表达克隆受体的中国仓鼠卵巢或COS-7细胞中，AVP刺激的磷脂酰肌醇水解和细胞内Ca 2+动员表明第二信使信号通过磷脂酶C。RNA印迹分析，逆转录PCR和原位杂交研究表明，V1 b受体mRNA表达在大多数垂体促肾上腺皮质激素以及在多个脑区和一些外周组织，包括肾脏，胸腺，心脏，肺，脾脏，子宫和乳腺。因此，V1 b受体必须介导AVP在垂体和其他器官中的一些不同生物学效应。
[Arg(8)]vasopressin (AVP) stimulates adrenocorticotropic hormone release from the anterior pituitary by acting on the V1b AVP receptor. This receptor can be distinguished from the vascular/hepatic V1a and renal V2 AVP receptors by its differential binding affinities for structural analogous of AVP. Recent studies have shown that the cloned Via and V2 receptors are structurally related. We have isolated a clone encoding the V1b receptor from a rat pituitary cDNA library using polymerase chain reaction (PCR)-based methodology. The rat V1b receptor is a protein of 421 amino acids that has 37-50% identity with the Via and V2 receptors. Homology is particularly high in the seven putative membrane-spanning domains of these guanine nucleotide-binding protein-coupled receptors. Expression of the recombinant receptor in mammalian cells shows the same binding specificity for AVP agonists and antagonists as the rat pituitary V1b receptor. AVP-stimulated phosphotidylinositol hydrolysis and intracellular Ca2+ mobilization in Chinese hamster ovary or COS-7 cells expressing the cloned receptor suggest second messenger signaling through phospholipase C. RNA blot analysis, reverse transcription PCR, and in situ hybridization studies reveal that V1b receptor mRNA is expressed in the majority of pituitary corticotropes as well as in multiple brain regions and a number of peripheral tissues, including kidney, thymus, heart, lung, spleen, uterus, and breast. Thus, the V1b receptor must mediate some of the diverse biological effects of AVP in the pituitary as well as other organs.