Molecular pharmacology of human vasopressin receptors.
Molecular pharmacology of human vasopressin receptors.
复制标题
人加压素受体的分子药理学。
DOI：
10.1007/978-1-4615-4871-3_34
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发表时间：
1998
影响因子：
--
通讯作者：
Mattera,R
中科院分区：
文献类型：
--
作者：
Thibonnier,M;Conarty,DM;Preston,JA;Wilkins,PL;Berti-Mattera,LN;Mattera,R
加压素(AVP)和催产素(OT)是通过激活特异性G蛋白偶联受体(GPCRs)发挥作用的环状非肽，目前分为V1-血管(V1R)、V2-肾(V2R)和V3-垂体(V3R)AVP受体和OT受体(OTR)。随着AVP/OT受体家族不同成员的克隆，稳定表达于CHO细胞中的人V1-血管(CHO-V1)、V2-肾(CHO-V2)、V3-垂体(CHO-V3)和催产素(CHO-OT)受体与18个多肽和5个非多肽AVP/OT类似物显示出不同的结合特征。一些多肽和非多肽化合物对V1R的亲和力比AVP本身更大。V2R多肽激动剂和拮抗剂往往是非选择性配体，而非肽V2R拮抗剂是有效的和亚型选择性的。在测试的22个AVP/OT类似物中，没有一个比AVP本身对人类V3R具有更好的亲和力。一些多肽拮抗剂不能很好地在V1R和OTR之间进行选择。这些结果强调了开发特定和有效的类似物与特定的人AVP/OT受体亚型特异性相互作用的必要性。
Vasopressin (AVP) and oxytocin (OT) are cyclic nonapeptides whose actions are mediated by activation of specific G protein-coupled receptors (GPCRs) currently classified into V1-vascular (V1R), V2-renal (V2R) and V3-pituitary (V3R) AVP receptors and OT receptors (OTR). The cloning of the different members of the AVP/OT family of receptors now allows the extensive molecular pharmacological characterization of a single AVP/OT receptor subtype in stably transfected mammalian cell lines.The human V1-vascular (CHO-V1), V2-renal (CHO-V2), V3-pituitary (CHO-V3) and oxytocin (CHO-OT) receptors stably expressed in CHO cells display distinct binding profiles for 18 peptide and 5 nonpeptide AVP/OT analogs. Several peptide and nonpeptide compounds have a greater affinity for the V1R than AVP itself. V2R peptide agonists and antagonists tend to be non-selective ligands whereas nonpeptide V2R antagonists are potent and subtype-selective. None of the 22 AVP/OT analogs tested has a better affinity for the human V3R than AVP itself. Several peptide antagonists do not select well between V1R and OTR. These results underscore the need for developing specific and potent analogs interacting specifically with a given human AVP/OT receptor subtype.