Uridine adenosine tetraphosphate induces contraction of circular and longitudinal gastric smooth muscle by distinct signaling pathways

Yuan, Wensu; Wang, Zengyong; Li, Jingjing; Liu, Dong; Liu, Deliang; Bai, Gang; Walsh, Michael P.; Gui, Yu; Zheng, Xi-Long

doi:10.1002/iub.1171

Cited by 12 publications

(13 citation statements)

References 20 publications

(36 reference statements)

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“…Several subsequent studies have confirmed that Up 4 A produces vasoconstriction in rat renal artery (3), aorta (5), gastric smooth muscle (29) and pulmonary arteries (6). Furthermore, vasoconstriction was observed in mouse renal arterioles (7) and aorta (8).…”

Section: Discussionmentioning

confidence: 89%

Mechanisms underlying uridine adenosine tetraphosphate-induced vascular contraction in mouse aorta: Role of thromboxane and purinergic receptors

Zhou

Sun

Tilley

et al. 2015

Vascular Pharmacology

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Uridine adenosine tetraphosphate (Up4A), a novel endothelium-derived vasoactive agent, is proposed to play a role in cardiovascular disorders and induces aortic contraction through activation of cyclooxygenases (COX). We and others demonstrated that activation of A1 or A3 adenosine receptors (AR) results in vascular contraction via thromboxane (TX) A2 production. However, the mechanisms of Up4A-induced vascular contraction in mouse aorta are not understood. We hypothesize that Up4A-induced aortic contraction is through COX-derived TXA2 production, which requires activation of A1 and/or A3AR. Concentration responses to Up4A were conducted in isolated aorta. The TXB2 production, a metabolite of TXA2, was also measured. Up4A (10−9–10−5 M) produced a concentration-dependent contraction >70%, which was markedly attenuated by COX and COX1 but not by COX2 inhibition. Notably, Up4A-induced aortic contraction was blunted by both TX synthase inhibitor ozagrel and TXA2 receptor (TP) antagonist SQ29548. Surprisingly, A3AR deletion had no effect on Up4A-induced contraction. Moreover, A1AR deletion or antagonism as well as A1/A3AR deletion potentiated Up4A-induced aortic contraction, suggesting a vasodilator influence of A1AR. In contrast, non-selective purinergic P2 receptor antagonist PPADS significantly blunted Up4A-induced aortic contraction to a similar extent as selective P2X1R antagonist MRS2159, the latter of which was further reduced by addition of ozagrel. Endothelial denudation almost fully attenuated Up4A-induced contraction. Furthermore, Up4A (3 µM) increased TXB2 formation, which was inhibited by either MRS2159 or ozagrel. In conclusion, Up4A-induced aortic contraction depends on activation of TX synthase and TP, which partially requires the activation of P2X1R but not A1 or A3 AR through an endothelium-dependent mechanism.

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Section: Discussionmentioning

confidence: 89%

Mechanisms underlying uridine adenosine tetraphosphate-induced vascular contraction in mouse aorta: Role of thromboxane and purinergic receptors

Zhou

Sun

Tilley

et al. 2015

Vascular Pharmacology

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“…Up4A is likely associated with blood pressure regulation, because its levels in plasma are elevated in hypertensive subjects (3) and it causes vasoconstriction in deoxycorticosterone acetate-salt hypertensive rats (4) and type 2 diabetic rats (5). Up4A also contracts rat and human airways (6) and rat gastric smooth muscles (7). Pharmacological studies suggest that Up4A causes vasoconstriction via activation of P2X1, P2Y2, and P2Y4 receptors (1) and endothelium-dependent vasodilatation via activation of P2Y1 and P2Y2 receptors (8).…”

mentioning

confidence: 99%

Uridine adenosine tetraphosphate is a novel neurogenic P2Y1 receptor activator in the gut

Durnin

Hwang

Kurahashi

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…Cytidine-5′-diphosphocholine, an endogenous nucleotide, used for the treatment of neurodegenerative disorders, produced contractions of mouse gastric fundus through, at least in part, purinoceptors and Rho/Rho kinase signalling [303]. Uridine adenosine tetraphosphate produces contraction of gastric smooth muscle via P2Y receptors [744].…”

Section: Receptor Identificationmentioning

confidence: 99%

Purinergic signalling in the gastrointestinal tract and related organs in health and disease

Burnstock

2013

Purinergic Signalling

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Purinergic signalling plays major roles in the physiology and pathophysiology of digestive organs. Adenosine 5′-triphosphate (ATP), together with nitric oxide and vasoactive intestinal peptide, is a cotransmitter in nonadrenergic, non-cholinergic inhibitory neuromuscular transmission. P2X and P2Y receptors are widely expressed in myenteric and submucous enteric plexuses and participate in sympathetic transmission and neuromodulation involved in enteric reflex activities, as well as influencing gastric and intestinal epithelial secretion and vascular activities. Involvement of purinergic signalling has been identified in a variety of diseases, including inflammatory bowel disease, ischaemia, diabetes and cancer. Purinergic mechanosensory transduction forms the basis of enteric nociception, where ATP released from mucosal epithelial cells by distension activates nociceptive subepithelial primary afferent sensory fibres expressing P2X3 receptors to send messages to the pain centres in the central nervous system via interneurons in the spinal cord. Purinergic signalling is also involved in salivary gland and bile duct secretion.

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Uridine adenosine tetraphosphate induces contraction of circular and longitudinal gastric smooth muscle by distinct signaling pathways

Cited by 12 publications

References 20 publications

Mechanisms underlying uridine adenosine tetraphosphate-induced vascular contraction in mouse aorta: Role of thromboxane and purinergic receptors

Mechanisms underlying uridine adenosine tetraphosphate-induced vascular contraction in mouse aorta: Role of thromboxane and purinergic receptors

Uridine adenosine tetraphosphate is a novel neurogenic P2Y1 receptor activator in the gut

Purinergic signalling in the gastrointestinal tract and related organs in health and disease

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