P2Y Purinergic Receptors, Endothelial Dysfunction, and Cardiovascular Diseases

Purinergic G-protein-coupled receptors are ancient and the most abundant group of G-protein-coupled receptors (GPCRs). The wide distribution of purinergic receptors in the cardiovascular system, together with the expression of multiple receptor subtypes in endothelial cells (ECs) and other vascular cells demonstrates the physiological importance of the purinergic signaling system in the regulation of the cardiovascular system. This review discusses the contribution of purinergic P2Y receptors to endothelial dysfunction (ED) in numerous cardiovascular diseases (CVDs). Endothelial dysfunction can be defined as a shift from a “calm” or non-activated state, characterized by low permeability, anti-thrombotic, and anti-inflammatory properties, to a “activated” state, characterized by vasoconstriction and increased permeability, pro-thrombotic, and pro-inflammatory properties. This state of ED is observed in many diseases, including atherosclerosis, diabetes, hypertension, metabolic syndrome, sepsis, and pulmonary hypertension. Herein, we review the recent advances in P2Y receptor physiology and emphasize some of their unique signaling features in pulmonary endothelial cells.

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GRKs as Modulators of Neurotransmitter Receptors

Cells ◽

10.3390/cells10010052 ◽

2020 ◽

Vol 10 (1) ◽

pp. 52

Author(s):

Eugenia V. Gurevich ◽

Vsevolod V. Gurevich

Keyword(s):

G Protein ◽

General Model ◽

G Protein Coupled Receptors ◽

Receptor Internalization ◽

Neurotransmitter Receptors ◽

Receptor Subtype ◽

Receptor Subtypes ◽

Receptor Kinase ◽

G Protein Coupled ◽

Homologous Desensitization

Many receptors for neurotransmitters, such as dopamine, norepinephrine, acetylcholine, and neuropeptides, belong to the superfamily of G protein-coupled receptors (GPCRs). A general model posits that GPCRs undergo two-step homologous desensitization: the active receptor is phosphorylated by kinases of the G protein-coupled receptor kinase (GRK) family, whereupon arrestin proteins specifically bind active phosphorylated receptors, shutting down G protein-mediated signaling, facilitating receptor internalization, and initiating distinct signaling pathways via arrestin-based scaffolding. Here, we review the mechanisms of GRK-dependent regulation of neurotransmitter receptors, focusing on the diverse modes of GRK-mediated phosphorylation of receptor subtypes. The immediate signaling consequences of GRK-mediated receptor phosphorylation, such as arrestin recruitment, desensitization, and internalization/resensitization, are equally diverse, depending not only on the receptor subtype but also on phosphorylation by GRKs of select receptor residues. We discuss the signaling outcome as well as the biological and behavioral consequences of the GRK-dependent phosphorylation of neurotransmitter receptors where known.

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Nucleoligands-repurposing G Protein–coupled Receptor Ligands to Modulate Nuclear-localized G Protein–coupled Receptors in the Cardiovascular System

Journal of Cardiovascular Pharmacology ◽

10.1097/fjc.0000000000000535 ◽

2018 ◽

Vol 71 (4) ◽

pp. 193-204 ◽

Cited By ~ 3

Author(s):

Nicolas Audet ◽

Rabah Dabouz ◽

Bruce G. Allen ◽

Terence E. Hébert

Keyword(s):

Cardiovascular System ◽

G Protein ◽

G Protein Coupled Receptors ◽

Receptor Ligands ◽

G Protein Coupled Receptor ◽

G Protein Coupled

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G protein-coupled receptors sense fluid shear stress in endothelial cells

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.0607224103 ◽

2006 ◽

Vol 103 (42) ◽

pp. 15463-15468 ◽

Cited By ~ 288

Author(s):

M. Chachisvilis ◽

Y.-L. Zhang ◽

J. A. Frangos

Keyword(s):

Endothelial Cells ◽

Shear Stress ◽

G Protein ◽

Fluid Shear Stress ◽

G Protein Coupled Receptors ◽

Fluid Shear ◽

G Protein Coupled

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Markers of endothelial dysfunction

Regional blood circulation and microcirculation ◽

10.24884/1682-6655-2017-16-1-4-15 ◽

2017 ◽

Vol 16 (1) ◽

pp. 4-15 ◽

Cited By ~ 12

Author(s):

L. V. Vasina ◽

N. N. Petrishchev ◽

T. D. Vlasov

Keyword(s):

Endothelial Cells ◽

Cardiovascular Diseases ◽

Endothelial Dysfunction ◽

Cardiovascular System ◽

Endothelial Damage ◽

Morphological Heterogeneity

Endothelial dysfunction is considered as a universal non-specific link in the pathogenesis of many diseases, primarily the cardiovascular system. This review is devoted to the discussion of the main functions of the endothelium and mechanisms for their implementation. One of the most striking features of endothelial cells is their morphological heterogeneity, which allows us to identify several typical forms of endothelial dysfunction (vasomotor, hemostatic, adhesion and angiogenous). Also, the review presents the most promising predictors of cardiovascular diseases and their complications among endothelial damage markers.

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