MOLECULAR-CLONING OF A FUNCTIONAL HUMAN GALANIN RECEPTOR
MOLECULAR-CLONING OF A FUNCTIONAL HUMAN GALANIN RECEPTOR
复制标题
DOI：
10.1073/pnas.91.21.9780
复制
发表时间：
1994-10-11
影响因子：
11.1
通讯作者：
MAYAUX, JF
中科院分区：
文献类型：
--
作者：
HABERTORTOLI, E;AMIRANOFF, B;MAYAUX, JF
普遍存在的神经肽甘丙肽控制着多种功能，如内分泌分泌、肠道蠕动和行为活动。甘丙肽的这些调节作用是通过与特定膜受体的相互作用介导的，并涉及百日咳毒素敏感的鸟嘌呤核苷酸结合蛋白 G(i)/G(o) 作为转导元件。我们在这里报道了通过使用放射性配体结合策略从 Bowes 黑色素瘤细胞系 cDNA 表达文库中分离出编码人甘丙肽受体的 cDNA。克隆受体的核苷酸序列揭示了编码349个氨基酸的蛋白质的开放阅读框，该蛋白质具有7个假定的疏水性跨膜结构域，并且与鸟嘌呤核苷酸结合蛋白偶联神经肽受体家族的成员具有显着同源性。在COS细胞中表达的克隆受体以高亲和力（K-d在纳摩尔范围内）特异性结合人、猪和大鼠甘丙肽，并介导甘丙肽对腺苷酸环化酶的抑制。在几种人体组织中鉴定出 2.8-kb 甘丙肽受体转录物。这种甘丙肽受体的克隆应该增强我们对其在人体生理学和病理生理学中的分布、结构和功能的了解。
The ubiquitous neuropeptide galanin controls numerous functions such as endocrine secretions, intestinal motility, and behavioral activities. These regulatory effects of galanin are mediated through the interaction with specific membrane receptors and involve the pertussis toxin-sensitive guanine nucleotide binding proteins G(i)/G(o) as transducing elements. We report here the isolation of a cDNA coding for a human galanin receptor from a Bowes melanoma cell line cDNA expression library, by using a radioligand binding strategy. The nucleotide sequence of the cloned receptor reveals an open reading frame encoding a 349-amino acid protein with seven putative hydrophobic transmembrane domains and significant homology with members of the guanine nucleotide binding protein-coupled neuropeptide receptor family, The cloned receptor expressed in COS cells specifically binds human, porcine, and rat galanin with high affinity (K-d in the nanomolar range) and mediates the galanin inhibition of adenylate cyclase. A 2.8-kb galanin receptor transcript was identified in several human tissues. Cloning of this galanin receptor should enhance our knowledge of its distribution, structure, and function in human physiology and pathophysiology.