Purinergic Signaling During Hyperglycemia in Vascular Smooth Muscle Cells
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The activation of purinergic receptors by nucleotides and/or nucleosides plays an important role in the control of vascular function, including modulation of vascular smooth muscle excitability, and vascular reactivity. Accordingly, purinergic receptor actions, acting as either ion channels (P2X) or G protein-coupled receptors (GCPRs) (P1, P2Y), target diverse downstream effectors, and substrates to regulate vascular smooth muscle function and vascular reactivity. Both vasorelaxant and vasoconstrictive effects have been shown to be mediated by different purinergic receptors in a vascular bed- and species-specific manner. Purinergic signaling has been shown to play a key role in altering vascular smooth muscle excitability and vascular reactivity following acute and short-term elevations in extracellular glucose (e.g., hyperglycemia). Moreover, there is evidence that vascular smooth muscle excitability and vascular reactivity is severely impaired during diabetes and that this is mediated, at least in part, by activation of purinergic receptors. Thus, purinergic receptors present themselves as important candidates mediating vascular reactivity in hyperglycemia, with potentially important clinical and therapeutic potential. In this review, we provide a narrative summarizing our current understanding of the expression, function, and signaling of purinergic receptors specifically in vascular smooth muscle cells and discuss their role in vascular complications following hyperglycemia and diabetes. © Copyright © 2020 Martin-Aragon Baudel, Espinosa-Tanguma, Nieves-Cintron and Navedo.
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diabetes; ion channels; myogenic tone; P2Y11; purinergic receptors; vascular reactivity adenosine receptor; calcium channel; calcium release activated calcium channel 1; connexin 43; cyclic GMP; glucose; guanylate cyclase; nerve growth factor; neuropeptide Y; nitric oxide; noradrenalin; phenylephrine; potassium channel; purinergic P2X1 receptor; purinergic P2X7 receptor; purinergic P2Y11 receptor; streptozocin; action potential; angiogenesis; blood vessel reactivity; calcium signaling; chloride current; diabetes mellitus; diet-induced obesity; exercise; glucose homeostasis; glucose transport; human; hyperglycemia; hyperpolarization; immunofluorescence; membrane depolarization; mitogenesis; muscle function; muscle relaxation; natural killer cell; obesity; osmotic stress; protein expression; Review; sensory nerve cell; signal transduction; thrombocyte aggregation; upregulation; vascular smooth muscle cell; vasodilatation
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