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The Human V3 Pituitary Vasopressin Receptor: Ligand Binding Profile and Density-Dependent Signaling Pathways

The Human V3 Pituitary Vasopressin Receptor: Ligand Binding Profile and Density-Dependent Signaling Pathways,10.1210/en.138.10.4109,Endocrinology,MARC

The Human V3 Pituitary Vasopressin Receptor: Ligand Binding Profile and Density-Dependent Signaling Pathways   (Citations: 39)
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The vasopressin (AVP) V3 pituitary receptor (V3R) is a G protein- coupled corticotropic phenotypic marker that is overexpressed in ACTH-hypersecreting tumors. Studies of the agonist/antagonist bind- ing profile and signal transduction pathways linked to the human V3R have been limited because of the scarcity of this protein. To define the signals activated by V3Rs and the eventual changes triggered by developmental or pathological receptor regulation, we developed Chi- nese hamster ovary (CHO)-V3 cells stably expressing low, medium, or high levels of human V3Rs (binding capacity, ,10, 10 -25, and 25-100 pmol/mg, respectively). The affinity of the V3R for 21 peptide and nonpeptide AVP analogs was clearly distinct from that exhibited by the human V1R and V2R. AVP triggered stimulation of phospholipase C in CHO-V3 cells (par- tially sensitive to treatment with pertussis toxin) with a potency directly proportional to receptor density. V3R-mediated arachidonic acid release also was also sensitive to pertussis toxin and more effi- cacious in cells exhibiting medium than in those with high receptor density. AVP also stimulated the pertussis toxin-insensitive uptake of (3H)thymidine in CHO-V3 cells. The concentration-response curves for this effect were monophasic in cells expressing low and medium levels of V3Rs; on the contrary, a biphasic curve was observed in cells with high V3R density. Coupling of V3R to increased production of cAMP was only observed in CHOV3 high cells, suggesting a negative relationship between increased cAMP production and DNA synthesis. Activation of mitogen-activated protein kinases by V3R was pertussis toxin insensitive, but was dependent on activation of phospholipase C and protein kinase C; both the level and duration of activation were a function of the receptor density. Thus, the human V3R has a pharmacological profile clearly distinct from that of the human V1R and V2R and activates several signaling pathways via different G proteins, depending on the level of receptor expression. The increased synthesis of DNA and cAMP levels ob- served in cells expressing medium and high levels of V3Rs, respec- tively, may represent important events in the tumorigenesis of cor- ticotroph cells. (Endocrinology 138: 4109 - 4122, 1997)
Journal: Endocrinology , vol. 138, no. 10, pp. 4109-4122, 1997
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    • ...Alternatively, the increased V1bR gene expression in SCA may be related to its tumor growth because vasopressin can also activate cAMP formation and phosphorylation of MAP kinases to induce mitogenic effects in cell lines overexpressing human V1bR (14)...

    Toru Tatenoet al. Differential gene expression in ACTH -secreting and non-functioning pi...

    • ...However, the V 3 R has a pharmacologic profile that distinguishes it from the human V 1 R and activates several signaling pathways via different Gproteins, depending on the level of receptor expression [68]...
    • ...For instance, vasopressin causes secretion of ACTH from the anterior pituitary cells in a dose-dependent manner through activation of PKC [70] via the G q/11 class [68]...
    • ...Other cellular responses, including increased synthesis of DNA and cAMP, which are important in the induction and phenotype maintenance of ACTH-secreting tumors, are mediated through recruitment of several pathways, including G s , G i , and Gq/11 [68]...

    Cheryl L Holmeset al. Science Review: Vasopressin and the cardiovascular system part 1 – rec...

    • ...The antagonist used is able to distinguish between V1 and V2 AVP receptors, but not between the V1 receptor subtypes (Thibonnier et al. 1997)...

    M Hatzingeret al. Endogenous vasopressin contributes to hypothalamic-pituitary-adrenocor...

    • ... The rank order of affinity of the reference peptide and nonpeptide compounds tested indicated that the homogenous population of sites labeled by &lsqb3H]-SR 121463 exhibited the expected profile for human AVP V2 receptors Table 2, in good agreement with published values using &lsqb3H]-AVP as a ligan...

    Claudine Serradeil-Le Galet al. Binding properties of a selective tritiated vasopressin V2 receptor an...

    • ...In conclusion, the pharmacology of the cloned receptor corresponds to a V3/V1b profile and is in good agreement with the data reported in the literature, including relevant species diVerences (de Keyzer et al. 1994, Sugimoto et al. 1994, Lolait et al. 1995, Saito et al. 1995, Thibonnier et al. 1997, Burbach et al. 1995, Barberis & Tribollet 1996)...

    M A Venturaet al. Gene and cDNA cloning and characterization of the mouse V3/V1b pituita...

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