UDP-Sugars as Extracellular Signaling Molecules: Cellular and Physiologic Consequences of P2Y<sub>14</sub> Receptor Activation

Lazarowski, Eduardo R.; Harden, T. Kendall

doi:10.1124/mol.115.098756

Cited by 89 publications

(102 citation statements)

References 65 publications

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“…The P2Y 14 R is a Gi-coupled receptor that is activated by UDP-sugars with a relative potency order of UDP-glucose > UDP-galactose > UDP-glucuronic acid > UDP-Nacetylglucosamine [13,14]. UDP also is an agonist of this receptor, but ATP, UTP, or other naturally occurring nucleoside 5′-di-or triphosphates have no P2Y 14 R activity [13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

“…UDP also is an agonist of this receptor, but ATP, UTP, or other naturally occurring nucleoside 5′-di-or triphosphates have no P2Y 14 R activity [13][14][15][16]. P2Y 14 R mRNA expression has been reported in the brain and several peripheral tissues [13], including the lung, circulating neutrophils, and other immune/inflammatory cells [17][18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

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UDP-glucose promotes neutrophil recruitment in the lung

Sesma

Weitzer

Livraghi‐Butrico

et al. 2016

Purinergic Signalling

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In addition to their role in glycosylation reactions, UDP-sugars are released from cells and activate widely distributed cell surface P2Y 14 receptors (P2Y 14 R). However, the physiological/pathophysiological consequences of UDPsugar release are incompletely defined. Here, we report that UDP-glucose levels are abnormally elevated in lung secretions from patients with cystic fibrosis (CF) as well as in a mouse model of CF-like disease, the βENaC transgenic (Tg) mouse. Instillation of UDP-glucose into wild-type mouse tracheas resulted in enhanced neutrophil lung recruitment, and this effect was nearly abolished when UDP-glucose was coinstilled with the P2Y 14 R antagonist PPTN [4-(piperidin-4-yl)-phenyl)-7-(4-(trifluoromethyl)-phenyl-2-naphthoic acid]. Importantly, administration of PPTN to βENaC-Tg mice reduced neutrophil lung inflammation. These results suggest that UDP-glucose released into the airways acts as a local mediator of neutrophil inflammation.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

UDP-glucose promotes neutrophil recruitment in the lung

Sesma

Weitzer

Livraghi‐Butrico

et al. 2016

Purinergic Signalling

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“…32 To date, a clear role for this receptor has only been established in human neutrophils, where it contributes to chemotaxis. 80 Further studies will be required to evaluate its role in various inflammatory situations.…”

Section: P2y 14 Receptormentioning

confidence: 99%

Purinergic Receptors in Thrombosis and Inflammation

Hechler

Gachet

2015

ATVB

142

101

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Abstract-Under various pathological conditions, including thrombosis and inflammation, extracellular nucleotide levels may increase because of both active release and passive leakage from damaged or dying cells. Once in the extracellular compartment, nucleotides interact with plasma membrane receptors belonging to the P2 purinergic family, which are expressed by virtually all circulating blood cells and in most blood vessels. In this review, we focus on the specific role of the 3 platelet P2 receptors P2Y 1 , P2Y 12 , and P2X 1 in hemostasis and arterial thrombosis. Beyond platelets, these 3 receptors, along with the P2Y 2 , P2Y 6 , and P2X 7 receptors, constitute the main P2 receptors mediating the proinflammatory effects of nucleotides, which play important roles in various functions of circulating blood cells and cells of the vessel wall. Each of these P2 receptor subtypes specifically contributes to chronic or acute vascular inflammation and related diseases, such as atherosclerosis, restenosis, endotoxemia, and sepsis. The potential for therapeutic targeting of these P2 receptor subtypes is also discussed.

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“…The P2Y14 receptor subtype, the only officially-recognized P2Y purinergic receptor activated by uridine sugars (i.e. UDP-glucose and UDP-galactose) which is expressed by leukocytes and promotes neutrophil chemotaxis (Lazarowski et al, 2015), has been found upregulated in spinal microglia after peripheral nerve injury (Kobayashi et al, 2012). The demonstration that its activation on microglia cells reduced the proliferation of astrocytoma cells in in vitro cocultures (Curet & Watters, 2018) suggests that it may represent an additional member of the purinergic network controlling astrocyte-to-microglia communication in the brain in pathological conditions, possibly including pain.…”

Section: Contribution Of Spinal Astrocytes To Neuropathic Pain: a Rolmentioning

confidence: 99%

The role of adenosine and P2Y receptors expressed by multiple cell types in pain transmission

Magni

Ceruti

2019

Brain Research Bulletin

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The role of extracellular nucleotides and nucleosides as signaling molecules in cell-to-cell communication has now been clearly established. This is particularly true in the central and peripheral nervous system, where purines and pyrimidines are involved in both physiological and pathological interactions between neurons and surrounding glial cells. It can be thus foreseen that the purinergic system could represent a new potential target for the development of effective analgesics, also through the normalization of neuronal functions and the inhibition of glial cell activation. Research in the last 15 years has progressively confirmed this hypothesis, but no purinergic-based analgesics have reach the market so far; in the present review we have collected the more recent discoveries on the role of G protein-coupled P2Y nucleotide and of adenosine receptors expressed by both neurons and glial cells under painful conditions, and we have highlighted some of the challenges that must be faced to translate basic and preclinical studies to clinics.

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UDP-Sugars as Extracellular Signaling Molecules: Cellular and Physiologic Consequences of P2Y₁₄ Receptor Activation

Cited by 89 publications

References 65 publications

UDP-glucose promotes neutrophil recruitment in the lung

UDP-glucose promotes neutrophil recruitment in the lung

Purinergic Receptors in Thrombosis and Inflammation

The role of adenosine and P2Y receptors expressed by multiple cell types in pain transmission

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UDP-Sugars as Extracellular Signaling Molecules: Cellular and Physiologic Consequences of P2Y14 Receptor Activation

Cited by 89 publications

References 65 publications

UDP-glucose promotes neutrophil recruitment in the lung

UDP-glucose promotes neutrophil recruitment in the lung

Purinergic Receptors in Thrombosis and Inflammation

The role of adenosine and P2Y receptors expressed by multiple cell types in pain transmission

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Product

Resources

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UDP-Sugars as Extracellular Signaling Molecules: Cellular and Physiologic Consequences of P2Y₁₄ Receptor Activation