Expression and localization of pannexin‐1 hemichannels in human colon in health and disease

Diezmos, Erica F.; Sandow, Shaun L.; Markus, Irit; Perera, D. S.; Lubowski, David Z.; King, D. W.; Bertrand, Paul; Liu, L.

doi:10.1111/nmo.12130

Cited by 39 publications

(47 citation statements)

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“…In addition, other nonvascular SMCs release ATP, including SMCs from the colon (59) and SMCs from the bladder (60). Although the mechanisms of ATP liberation from those cells are still under investigation, pannexins are present in these nonvascular SMCs (61, 62). …”

Section: Discussionmentioning

confidence: 99%

A molecular signature in the pannexin1 intracellular loop confers channel activation by the α1 adrenoreceptor in smooth muscle cells

et al. 2015

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Both purinergic signaling through nucleotides such as ATP (adenosine 5′-triphosphate) and noradrenergic signaling through molecules such as norepinephrine regulate vascular tone and blood pressure. Pannexin1 (Panx1), which forms large-pore, ATP-releasing channels, is present in vascular smooth muscle cells in peripheral blood vessels and participates in noradrenergic responses. Using pharmacological approaches and mice conditionally lacking Panx1 in smooth muscle cells, we found that Panx1 contributed to vaso-constriction mediated by the α1 adrenoreceptor (α1AR), whereas vasoconstriction in response to serotonin or endothelin-1 was independent of Panx1. Analysis of the Panx1-deficient mice showed that Panx1 contributed to blood pressure regulation especially during the night cycle when sympathetic nervous activity is highest. Using mimetic peptides and site-directed mutagenesis, we identified a specific amino acid sequence in the Panx1 intracellular loop that is essential for activation by α1AR signaling. Collectively, these data describe a specific link between noradrenergic and purinergic signaling in blood pressure homeostasis.

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Section: Discussionmentioning

confidence: 99%

A molecular signature in the pannexin1 intracellular loop confers channel activation by the α1 adrenoreceptor in smooth muscle cells

et al. 2015

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“…Hemichannels containing pannexins may act as conduits for ATP release from non-neuronal cells in response to physiological and pathological stimuli. These channels are able to form signalling complexes with the purinergic P2X7 receptor, which activation leads to large pore formation and consequently to further release of ATP [65, 66]. These authors proposed a model where high extracellular levels of ATP chronically activate neuronal P2X7, pannexins, and caspases.…”

Section: Discussionmentioning

confidence: 99%

Feed-Forward Inhibition of CD73 and Upregulation of Adenosine Deaminase Contribute to the Loss of Adenosine Neuromodulation in Postinflammatory Ileitis

Vieira

Magalhães-Cardoso

Ferreirinha

et al. 2014

Mediators of Inflammation

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Purinergic signalling is remarkably plastic during gastrointestinal inflammation. Thus, selective drugs targeting the “purinome” may be helpful for inflammatory gastrointestinal diseases. The myenteric neuromuscular transmission of healthy individuals is fine-tuned and controlled by adenosine acting on A2A excitatory receptors. Here, we investigated the neuromodulatory role of adenosine in TNBS-inflamed longitudinal muscle-myenteric plexus of the rat ileum. Seven-day postinflammation ileitis lacks adenosine neuromodulation, which may contribute to acceleration of gastrointestinal transit. The loss of adenosine neuromodulation results from deficient accumulation of the nucleoside at the myenteric synapse despite the fact that the increases in ATP release were observed. Disparity between ATP outflow and adenosine deficit in postinflammatory ileitis is ascribed to feed-forward inhibition of ecto-5′-nucleotidase/CD73 by high extracellular ATP and/or ADP. Redistribution of NTPDase2, but not of NTPDase3, from ganglion cell bodies to myenteric nerve terminals leads to preferential ADP accumulation from released ATP, thus contributing to the prolonged inhibition of muscle-bound ecto-5′-nucleotidase/CD73 and to the delay of adenosine formation at the inflamed neuromuscular synapse. On the other hand, depression of endogenous adenosine accumulation may also occur due to enhancement of adenosine deaminase activity. Both membrane-bound and soluble forms of ecto-5′-nucleotidase/CD73 and adenosine deaminase were detected in the inflamed myenteric plexus. These findings provide novel therapeutic targets for inflammatory gut motility disorders.

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“…Panx1 forms large pore channels permeable to ions and small molecules, and is a clinically relevant protein in inflammatory conditions (Kanneganti et al, 2007; Silverman et al, 2009; Gulbransen et al, 2012; Diezmos et al, 2013), stroke (Thompson et al, 2006; Bargiotas et al, 2011; Bargiotas et al, 2012; Dvoriantchikova et al, 2012), and cancer (Lai et al, 2007; Cowan et al, 2012; Penuela et al, 2012). Panx1 is ubiquitously found in many cell and tissue types throughout the body, while Panx2 and Panx3 exhibit slightly more restricted organ and tissue expression patterns.…”

Section: What Is the Value Of Unraveling The Panx1 Signalome?mentioning

confidence: 99%

The emerging Pannexin 1 signalome: a new nexus revealed?

Wicki-Stordeur

Swayne²

2014

Front. Cell. Neurosci.

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Pannexins (Panxs) are a family of single-membrane, large-pore ion, and metabolite permeable channels. Of the three Panx proteins, Panx1 has been most extensively studied, and has recently emerged as an exciting, clinically relevant target in many physiological and pathophysiological settings. This channel is widely expressed across various cell and tissue types; however its links to precise signaling pathways are largely unknown. Here we review the current literature surrounding presently identified Panx1–protein interactions, a critical first step to unraveling the Panx1 signalome. First we elucidate the reported associations of Panx1 with other ion channels, receptors, and channel signaling complexes. Further, we highlight recently identified Panx1–cytoskeleton interactions. Finally, we discuss the implications of these protein–protein interactions for Panx1 function in various cell and tissue types, and identify key outstanding questions arising from this work.

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Expression and localization of pannexin‐1 hemichannels in human colon in health and disease

Abstract: The presence of Panx1 in the colon and changes to its distribution in disease suggests that Panx1 channels may play an important role in mediating gut function and in IBD pathophysiology.

Cited by 39 publications

References 50 publications

A molecular signature in the pannexin1 intracellular loop confers channel activation by the α1 adrenoreceptor in smooth muscle cells

A molecular signature in the pannexin1 intracellular loop confers channel activation by the α1 adrenoreceptor in smooth muscle cells

Feed-Forward Inhibition of CD73 and Upregulation of Adenosine Deaminase Contribute to the Loss of Adenosine Neuromodulation in Postinflammatory Ileitis

The emerging Pannexin 1 signalome: a new nexus revealed?

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