Derivatives of somatic cell hybrids which carry the human gene locus for nephrogenic diabetes insipidus (NDI) express functional vasopressin renal V2-type receptors.

Derivatives of somatic cell hybrids which carry the human gene locus for nephrogenic diabetes insipidus (NDI) express functional vasopressin renal V2-type receptors.
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携带肾性尿崩症 (NDI) 人类基因座的体细胞杂交体的衍生物表达功能性加压素肾 V2 型受体。

DOI:
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发表时间:
1990
影响因子:
4.8
通讯作者:
Falk Fahrenholz
Falk Fahrenholz
中科院分区:
生物学2区
文献类型:
--
作者:
David A. Jans;B. A. V. Oost;H. Ropers;Falk Fahrenholz

文献摘要

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家族性抗加压素肾性尿崩症(NDI)的基因定位于人类X染色体的一个小区域(Xq 28)。分析了一系列携带野生型人X染色体片段的仓鼠肺成纤维细胞和小鼠淋巴细胞系的加压素肾型V2受体表达,以检验NDI基因座可能与V2受体基因具有同一性的假设。V2受体结合活性和诱导cAMP的产生响应[精氨酸加压素(AVP)的所有细胞系携带野生型NDI基因座,在对照细胞系。AVP刺激cAMP的产生是浓度依赖性的,并且可以通过与V2-V1受体特异性拮抗剂共孵育几乎完全抑制。V2特异性激动剂[Mpa 1,Val 4,Sar 7]AVP在诱导携带NDI-DNA的细胞产生cAMP方面与AVP一样有效,而对其他激素如降钙素、催产素(小于10(-8)M)、异丙肾上腺素或催产素特异性激动剂没有反应。所有结果都与V2受体基因与NDI位点共定位的假设一致,支持这两个位点是同一个的观点。
The gene responsible for familial vasopressin-resistant nephrogenic diabetes insipidus (NDI) has been localized to a small region of the human X-chromosome (Xq28). A series of hamster lung fibroblast and mouse lymphocyte cell lines carrying fragments of the wild type human X-chromosome was analyzed for vasopressin renal-type V2 receptor expression, to test the hypothesis that the NDI locus may have identity with the V2 receptor gene. V2 receptor binding activity and induction of cAMP production in response to [Arg8] vasopressin (AVP) were exhibited by all cell lines carrying the wild type NDI locus, in contrast to control cell lines. AVP stimulation of cAMP production was concentration-dependent and could be almost completely inhibited by co-incubation with a V2-V1 receptor-specific antagonist. The V2-specific agonist [Mpa1,Val4,Sar7]AVP was as potent as AVP in inducing cAMP production by NDI-DNA-carrying cells, whereas no response was shown to other hormones such as calcitonin, oxytocin (less than 10(-8) M), isoproterenol, or an oxytocin-specific agonist. All results were consistent with the hypothesis that the V2 receptor gene co-localized with the NDI locus, supporting the view that the loci are one and the same.