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Vasopressin Receptors in Blood Vessels and Proliferation of Endotheliocytes

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Abstract—

Proliferative effects of vasopressin belong to the least studied field of molecular biochemistry of peptide hormones. At the same time, synthetic preparations of vasopressin are widely used in the treatment of vascular diseases and in oncology. In a number of cases, vasopressin has proliferative effects; however, emerging information about the antiproliferative properties of the hormone is currently being more actively discussed. Any proliferation is accompanied by tissue neovascularization. Two main types of vasopressin receptors are expressed in the blood vessels. In this regard, analysis of how the vasopressin effect works with access to mitogenic and secretory effects in blood vessel cells is topical. The review considers tissue-specific peculiarities of vasopressin receptor expression and recent data concerning the organization of signal transduction of hormonal reception. Attention is focused on smooth muscle cells and platelets expressing V1А-type receptors and on endotheliocytes expressing V2 vasopressin receptors. The structure of glycopeptides and enzymes playing the role of mediators in noncanonical transduction of the hormonal signal was analyzed in detail. Particular attention was paid to the molecular organization of platelet/endothelial cell adhesion protein (PECAM-1). The integral glycopeptide PECAM-1 performs simultaneously structural and signaling functions, converting the vasoconstrictor effect of V1А vasopressin receptors into the reaction of other membrane receptors and intracellular enzymes of blood vessels. The cytoplasmic department of PECAM-1 is involved in the inhibition of VEGFR-2 receptor of vascular endothelial growth factor (VEGF), the main stimulator of endotheliocyte proliferation. Intercellular dimers of PECAM-1 activate integrins. The integrin αVβ3 and von Willebrand factor are expressed in endotheliocytes. Multimeric molecules of von Willebrand factor are involved in cooperation between the endothelium and interstitium with local reorganization of the vascular network accompanying the repair of blood vessels in trauma and tumor progression. The von Willebrand factor aggregates the complexes of ανβ3 integrins with other ligands and membrane receptors of endotheliocytes and platelets, fixing the cells to the basement membrane. V1А vasopressin receptors activate VEGF secretion in platelets and proliferation of myocytes. V2 receptors stimulate exocytosis of Weibel–Palade bodies and secretion of von Willebrand factor in endotheliocytes, inducing chemotaxis of smooth muscle cells and endotheliocytes. Activated ανβ3 integrins physically interact with VEGFR-2 receptors of endotheliocytes and modulate the stimulation of angiogenic effects.

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Funding

This work was supported by the budgetary project of the Institute of Cytology and Genetics (Siberian Branch, Russian Academy of Sciences) No. 0259-2021-0014.

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  1. Federal Research Center Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, 630090, Novosibirsk, Russia

    I. I. Khegay

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Translated by A. Barkhash

Abbreviations: AKAP, A kinase anchoring protein; AKT, AKR thymoma oncogene; AVP, arginine–vasopressin; CRE, cAMP response element; CREB, cAMP response element binding protein; DDAVP, diamino D arginine–vasopressin; Epac, exchange factor activated by cAMP; ERK1/2, extracellular signal-regulated kinase; GPCR, G protein-coupled receptor; ITIM, immunoreceptor tyrosine based inhibitory motif; LVL, lysine–vasopressin; MAPK, mitogen-activated protein kinase; MEK, mitogen-activated protein kinase kinase; PECAM-1, platelet/endothelial cell adhesion molecule 1; RTK, receptor tyrosine kinase; SH2, Sarcoma Raus Homology 2; SHB, SH2 containing protein binding adapter; SHP, SH2 containing protein tyrosine phosphatase; VEGF, vascular endothelial growth factor; VEGFR2, vascular endothelial growth factor receptor 2.

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Khegay, I.I. Vasopressin Receptors in Blood Vessels and Proliferation of Endotheliocytes. Russ J Bioorg Chem 47, 815–827 (2021). https://doi.org/10.1134/S1068162021040129

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