Interaction of purinergic receptors with GPCRs, ion channels, tyrosine kinase and steroid hormone receptors orchestrates cell function

Bilbao, P.; Katz, S; Boland, Ricardo

doi:10.1007/s11302-011-9260-9

Cited by 12 publications

(6 citation statements)

References 135 publications

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“…Here we concentrate on purinergic signaling and present evidence that this signaling could fine-tune and coordinate pancreatic secretion on several fronts. Pancreatic ducts express several types of purinergic receptors including members from the G-protein coupled receptor families (adenosine, P2Y) and ligand-gated ion channels (P2X receptor) families (Novak, 2008 , 2011 ) that can potentially stimulate a variety of intracellular signaling pathways (Burnstock, 2007 ; Surprenant and North, 2009 ; Lenertz et al, 2011 ; Wiley et al, 2011 ; Bilbao et al, 2012 ). These receptors regulate pancreatic duct ion transport, mucin secretion, and survival of fibrogenic pancreatic stellate cells (Jung et al, 2004 ; Haanes et al, 2012 ).…”

Section: Purinergic Signalingmentioning

confidence: 99%

Acid-base transport in pancreas—new challenges

2013

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Along the gastrointestinal tract a number of epithelia contribute with acid or basic secretions in order to aid digestive processes. The stomach and pancreas are the most extreme examples of acid (H+) and base (HCO−3) transporters, respectively. Nevertheless, they share the same challenges of transporting acid and bases across epithelia and effectively regulating their intracellular pH. In this review, we will make use of comparative physiology to enlighten the cellular mechanisms of pancreatic HCO−3 and fluid secretion, which is still challenging physiologists. Some of the novel transporters to consider in pancreas are the proton pumps (H+-K+-ATPases), as well as the calcium-activated K+ and Cl− channels, such as KCa3.1 and TMEM16A/ANO1. Local regulators, such as purinergic signaling, fine-tune, and coordinate pancreatic secretion. Lastly, we speculate whether dys-regulation of acid-base transport contributes to pancreatic diseases including cystic fibrosis, pancreatitis, and cancer.

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Section: Purinergic Signalingmentioning

confidence: 99%

Acid-base transport in pancreas—new challenges

2013

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“…P2X receptors are involved in fast synaptic transmission, e.g., in the medial habenula, the hippocampus, and the cerebral cortex [7][8][9]. P1 and P2Y receptors mediate synaptic plasticity by interaction with ion channels and receptors in many (if not all) brain regions such as the hippocampus, the cerebellum, the striatum and cerebral cortex [10][11][12]. In the mouse olfactory bulb, evidence for functional expression of purinoceptors was published only recently (reviewed in [13]).…”

Section: Introductionmentioning

confidence: 99%

P2Y1 receptor activation by photolysis of caged ATP enhances neuronal network activity in the developing olfactory bulb

Fischer

Rotermund

Lohr

et al. 2011

Purinergic Signalling

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It has recently been shown that adenosine-5′-triphosphate (ATP) is released together with glutamate from sensory axons in the olfactory bulb, where it stimulates calcium signaling in glial cells, while responses in identified neurons to ATP have not been recorded in the olfactory bulb yet. We used photolysis of caged ATP to elicit a rapid rise in ATP and measured whole-cell current responses in mitral cells, the output neurons of the olfactory bulb, in acute mouse brain slices. Wide-field photolysis of caged ATP evoked an increase in synaptic inputs in mitral cells, indicating an ATP-dependent increase in network activity. The increase in synaptic activity was accompanied by calcium transients in the dendritic tuft of the mitral cell, as measured by confocal calcium imaging. The stimulating effect of ATP on the network activity could be mimicked by photo release of caged adenosine 5′-diphosphate, and was inhibited by the P2Y 1 receptor antagonist MRS 2179. Local photolysis of caged ATP in the glomerulus innervated by the dendritic tuft of the recorded mitral cell elicited currents similar to those evoked by wide-field illumination. The results indicate that activation of P2Y 1 receptors in the glomerulus can stimulate network activity in the olfactory bulb.

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“…UTP does not activate hP2Y 11 R ( Morrow et al, 2014 ) and P2Y 11 effects to NF546 ( Meis et al, 2010 ) in BON were rare. The hP2Y 4 R forms stable dimers and transfected P2Y 4 R and P2Y 6 R proteins can associate with P2Y1,2,4,6,11 receptors ( D’Ambrosi et al, 2006 , 2007 ; Bilbao et al, 2012 ). Therefore, specific dimers could be responding to UTP and not UTPγS or UDP.…”

Section: Discussionmentioning

confidence: 99%

UTP – Gated Signaling Pathways of 5-HT Release from BON Cells as a Model of Human Enterochromaffin Cells

et al. 2017

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Background: Enterochromaffin cells (EC) synthesize and release 5-HT and ATP to trigger or modulate gut neural reflexes and transmit information about visceral/pain sensation. Alterations in 5-HT signaling mechanisms may contribute to the pathogenesis of IBD or IBS, but the pharmacologic or molecular mechanisms modulating Ca2+-dependent 5-HT release are not understood. Previous studies indicated that purinergic signaling via ATP and ADP is an important mechanism in modulation of 5-HT release. However, EC cells also respond to UTP and UDP suggesting uridine triphosphate receptor and signaling pathways are involved as well. We tested the hypothesis that UTP is a regulator of 5-HT release in human EC cells.Methods: UTP signaling mechanisms were studied in BON cells, a human EC model, using Fluo-4/Ca2+imaging, patch-clamp, pharmacological analysis, immunohistochemistry, western blots and qPCR. 5-HT release was monitored in BON or EC isolated from human gut surgical specimens (hEC).Results: UTP, UTPγS, UDP or ATP induced Ca2+oscillations in BON. UTP evoked a biphasic concentration-dependent Ca2+response. Cells responded in the order of UTP, ATP > UTPγS > UDP >> MRS2768, BzATP, α,β-MeATP > MRS2365, MRS2690, and NF546. Different proportions of cells activated by UTP and ATP also responded to UTPγS (P2Y4, 50% cells), UDP (P2Y6, 30%), UTPγS and UDP (14%) or MRS2768 (<3%). UTP Ca2+responses were blocked with inhibitors of PLC, IP3R, SERCA Ca2+pump, La3+sensitive Ca2+channels or chelation of intracellular free Ca2+ by BAPTA/AM. Inhibitors of L-type, TRPC, ryanodine-Ca2+pools, PI3-Kinase, PKC or SRC-Kinase had no effect. UTP stimulated voltage-sensitive Ca2+currents (ICa), Vm-depolarization and inhibited IK (not IA) currents. An IKv7.2/7.3 K+ channel blocker XE-991 mimicked UTP-induced Vm-depolarization and blocked UTP-responses. XE-991 blocked IK and UTP caused further reduction. La3+ or PLC inhibitors blocked UTP depolarization; PKC inhibitors, thapsigargin or zero Ca2+buffer did not. UTP stimulated 5-HT release in hEC expressing TPH1, 5-HT, P2Y4/P2Y6R. Zero-Ca2+buffer augmented Ca2+responses and 5-HT release.Conclusion: UTP activates a predominant P2Y4R pathway to trigger Ca2+oscillations via internal Ca2+mobilization through a PLC/IP3/IP3R/SERCA Ca2+signaling pathway to stimulate 5-HT release; Ca2+influx is inhibitory. UTP-induced Vm-depolarization depends on PLC signaling and an unidentified K channel (which appears independent of Ca2+oscillations or Ica/VOCC). UTP-gated signaling pathways triggered by activation of P2Y4R stimulate 5-HT release.

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Interaction of purinergic receptors with GPCRs, ion channels, tyrosine kinase and steroid hormone receptors orchestrates cell function

Cited by 12 publications

References 135 publications

Acid-base transport in pancreas—new challenges

Acid-base transport in pancreas—new challenges

P2Y1 receptor activation by photolysis of caged ATP enhances neuronal network activity in the developing olfactory bulb

UTP – Gated Signaling Pathways of 5-HT Release from BON Cells as a Model of Human Enterochromaffin Cells

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