Saito M, Tahara A, Sugimoto T, Abe K, Furuichi K
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., 21 Miyukigaoka, Ibaraki 305-8585, Tsukuba, Japan.
Eur J Pharmacol. 2000 Aug 11;401(3):289-96. doi: 10.1016/s0014-2999(00)00465-9.
Vasopressin V(2) receptors at high-density and V(1B) receptors are candidates for the V(2)-like receptor, which evokes an increase in Ca(2+) when stimulated by the vasopressin V(2) receptor agonist 1-desamino-8-D-arginine vasopressin (dDAVP) in kidney inner medullary collecting duct. We compared the pharmacological characteristics of vasopressin V(2) and V(1B) receptors in Chinese hamster ovary (CHO) cells to those of vasopressin V(2)-like receptors in rat inner medullary collecting duct cells. The vasopressin V(1B) receptor-selective agonist [deamino-Cys(1), D-3-(Pyridyl)-Ala(2), Arg(8)]vasopressin (D3PVP) did not stimulate the Ca(2+) increase in high-density vasopressin V(2) receptor-expressing CHO cells, but did in inner medullary collecting duct cells. Moreover, the vasopressin V(1A)/V(2) receptor dual antagonist 4'-[(2-methyl-1,4,5,6-tetrahydroimidazo[4,5-d][1] benzazepin-6-yl)carbonyl] 2-phenylbenzanilide (YM087), which has no effect on vasopressin V(1B) receptors, did not block the Ca(2+) increase in inner medullary collecting duct cells when stimulated by dDAVP and D3PVP. On reverse transcription-polymerase chain reaction (RT-PCR) analysis of kidney, vasopressin V(1B) receptor mRNA was detected only in the medulla. We propose that the true nature of the vasopressin V(2)-like receptor in the inner medullary collecting duct is the vasopressin V(1B) receptor, rather than the vasopressin V(2) receptor expressed at high-density.
高密度的血管加压素V(2)受体和V(1B)受体是类V(2)受体的候选者，当在肾内髓集合管中受到血管加压素V(2)受体激动剂1-去氨基-8-D-精氨酸血管加压素（dDAVP）刺激时，该类V(2)受体可引起细胞内钙离子浓度（Ca(2+)）升高。我们比较了中国仓鼠卵巢（CHO）细胞中血管加压素V(2)和V(1B)受体与大鼠内髓集合管细胞中血管加压素类V(2)受体的药理学特性。血管加压素V(1B)受体选择性激动剂[脱氨基-Cys(1)，D-3-(吡啶基)-Ala(2)，Arg(8)]血管加压素（D3PVP）不会刺激表达高密度血管加压素V(2)受体的CHO细胞内Ca(2+)升高，但会刺激内髓集合管细胞内Ca(2+)升高。此外，对血管加压素V(1A)/V(2)受体具有双重拮抗作用的4'-[(2-甲基-1,4,5,6-四氢咪唑并[4,5-d][1]苯并氮杂卓-6-基)羰基] 2-苯基苯甲酰胺（YM087）对血管加压素V(1B)受体无作用，当受到dDAVP和D3PVP刺激时，它不会阻断内髓集合管细胞内Ca(2+)升高。在对肾脏进行逆转录-聚合酶链反应（RT-PCR）分析时，仅在髓质中检测到血管加压素V(1B)受体mRNA。我们提出，内髓集合管中血管加压素类V(2)受体的真实本质是血管加压素V(1B)受体，而非高密度表达的血管加压素V(2)受体。
