Histamine Induces ATP Release from Human Subcutaneous Fibroblasts, via Pannexin-1 Hemichannels, Leading to Ca2+ Mobilization and Cell Proliferation

One contribution of 16 to a discussion meeting issue 'Release of chemical transmitters from cell bodies and dendrites of nerve cells'. Extracellular adenosine triphosphate (ATP) serves as a signal for diverse physiological functions, including spread of calcium waves between astrocytes, control of vascular oxygen supply and control of ciliary beat in the airways. ATP can be released from cells by various mechanisms. This review focuses on channel-mediated ATP release and its main enabler, Pannexin1 (Panx1). Six subunits of Panx1 form a plasma membrane channel termed 'pannexon'. Depending on the mode of stimulation, the pannexon has large conductance (500 pS) and unselective permeability to molecules less than 1.5 kD or is a small (50 pS), chloride-selective channel. Most physiological and pathological stimuli induce the large channel conformation, whereas the small conformation so far has only been observed with exclusive voltage activation of the channel. The interaction between pannexons and ATP is intimate. The pannexon is not only the conduit for ATP, permitting ATP efflux from cells down its concentration gradient, but the pannexon is also modulated by ATP. The channel can be activated by ATP through both ionotropic P2X as well as metabotropic P2Y purinergic receptors. In the absence of a control mechanism, this positive feedback loop would lead to cell death owing to the linkage of purinergic receptors with apoptotic processes. A control mechanism preventing excessive activation of the purinergic receptors is provided by ATP binding (with low affinity) to the Panx1 protein and gating the channel shut.

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“…(i) Histamine-induced ATP release seems to follow the same pattern as described for bradykinin [91].…”

Section: Activation Of Pannexons In Physiological and Pathological Comentioning

confidence: 71%

ATP release through pannexon channels

Dahl

2015

Phil. Trans. R. Soc. B

203

169

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“…As the ATP catabolizes to ADP, it stimulates P2X and P2Y purinergic receptors, respectively, on the same neuron or other neurons. Interestingly, TRPv1 stimulation of non-neural cells [83,84] also results in CWP and ATP release, likely amplifying the stimulation of P2X and P2Y receptors on neurons, a process that has previously been demonstrated in intestinal fibroblasts [85] and keratinocytes [86] following tissue mechanotransduction.…”

Section: The Effect Of Dry Needling Mechanotransduction On Trpv1 Recementioning

confidence: 99%

“…However, given that MCs are primarily located in loose connective tissue, the cells effectively connect sensory afferents to blood and lymphatic vessels and therefore play a role in vasodilation by releasing histamine, heparin, leukotrienes and NO [80,102,105]. While MC degranulation also directly results in ATP release [102,105], histamine further stimulates ATP release from subcutaneous fibroblasts, amplifying P2X/P2Y and adenosine mediated pain reduction [83].…”

Section: The Effect Of Dry Needling Mechanotransduction On Mast Cellsmentioning

confidence: 99%

“…A number of studies have linked the physical stimulation of needles with the activation of stretchsensitive chloride channels on MCs, resulting in degranulation [83,[102][103][104]. Some factors initially released during degranulation such as cytokines, serotonin and SP result in discomfort and may add to the perception of de qi [80,102].…”

Section: The Effect Of Dry Needling Mechanotransduction On Mast Cellsmentioning

confidence: 99%

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Peripheral and Spinal Mechanisms of Pain and Dry Needling Mediated Analgesia: A Clinical Resource Guide for Health Care Professionals

Butts¹,

Dunning²

2016

Int J Phys Med Rehabil

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There are a number of biochemical, biomechanical, endocrinological and neurovascular mechanisms underpinning the anti-nociceptive and anti-inflammatory effects of dry needling (DN). While myofascial trigger points likely play a role in peripheral pain, a diagnostic tool for localizing them has not been validated, and DN studies that have targeted trigger points to elicit localized twitch responses have reported mixed results. Therefore, the mechanism responsible for DN-mediated analgesia may be more complicated. DN activates opioid-based pain reduction, mediated by endogenous cannabinoids and the sympathetic nervous system, and non-opioid pain relief via serotonin and norepinephrine from the brain stem. DN also triggers the hypothalamic-pituitary-adrenal axis centrally and the corticotropin releasing hormone-proopiomelanocortin-corticosteroid axis locally to inhibit cox-2, reducing inflammatory cytokines. Recent studies demonstrate that DN combined with mechanical and/or electrical stimulation may reverse PKC-mediated peripheral hyperalgesic priming by normalizing nociceptive channels, to include TRPV, ASIC, TTX and P2X/Y. Electrical DN (EDN) stimulates immune cells, fibroblasts and keratinocytes to release CGRP and substance-P, altering the stimulation of TTX receptors to reverse hyperalgesia. It also encourages the supraoptic nucleus to release oxytocin to quiet ASIC receptors peripherally and stimulate opioid interneurons spinally. Moreover, EDN inhibits ERK1/2 kinase pathways of inflammation in the spinal cord and stimulates Aδ fibers and N/OFQ to reverse C-fiber mediated central changes. Mechanotransduction of fibroblasts and peripheral nerves via TRPV1 and P2X/Y-mediated intracellular Ca 2+ wave propagation and subsequent activation of the nucleus accumbens inhibits spinal pain transmission via glycinergic and opioidergic interneurons. The increased ATP is metabolized to adenosine, which activates P1 purinergic receptors, events considered key to DN analgesia and rho kinase-based tissue remodeling. Mechanotransduction-mediated release of histamine further explains analgesia secondary to needling points distal to pain. DN-mediated analgesia is dependent on a number of synergistic physiologic events involving biochemical and mechanical processes in neural, connective and muscle tissue.

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“…Probenecid has been reported to block Panx1 currents and dye uptake in oocytes expressing the channel, with no effect on currents carried by Cx46 or Cx32 1 43 (a chimera of Cx32 containing the first extracellular loop of Cx43) [185]. In addition, probenecid reduced [Ca 2+ ] i in response to histamine in subcutaneous fibroblasts which was dependent on Panx1-mediated ATP release [186]. Cx hemichannels was assessed.…”

Section: Channelsmentioning

confidence: 99%

Function and Regulation of Pannexin 1 Channels in the Vascular Endothelium

Lohman¹

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The nucleotide adenosine 5'-triphosphate (ATP) has classically been considered the cell's primary energy currency; however, a novel role for ATP as an extracellular autocrine/paracrine signaling molecule has evolved over the past century. Purinergic signaling is now known to regulate a plethora of physiological and pathophysiological processes in almost every organ system. In the vasculature, ATP and its metabolites elicit dual control over blood vessel tone and tissue perfusion, and purinergic signaling events have been implicated in vascular pathologies including atherosclerosis and inflammation.While the importance of extracellular ATP in the vascular system is well recognized, the mechanism(s) mediating the regulated release of the purine from vascular cells are less well understood and are a key target of current investigation. One such ATP-liberation mechanism has been ascribed to the recently identified pannexin (Panx) channels, namely Panx1. Initially, we characterized the expression and localization profiles of Panx isoforms across the systemic vasculature, identifying predominant representation by the Panx1 isoform in both smooth muscle (SMC) and endothelial cells (EC) comprising the blood vessel wall, with more heterogeneous expression profiles observed in specialized vascular systems including the heart, lung and kidney. In particular, the Panx1 isoform is highly expressed in ECs regardless of blood vessel type or size, while Panx1 expression is limited to SMCs of small arteries and arterioles. Panx1 forms hexameric channels in the plasma membrane of ECs, functioning to release ATP in response to a number of stimuli. However, prolonged Panx1 channel activity is extremely detrimental to cell viability. Here we report a novel negative regulatory mechanism that may govern the activity of Panx1 channels in ECs, by which the bioactive gas nitric oxide (NO) covalently modifies two cysteine (Cys) residues in the channel by a process termed S- reinforce the dual effect of purines on peripheral resistance and blood pressure. Purinergic Control of Vascular InflammationWhile the foundation for purinergic control of vascular functions was initially characterized extensively in the context of vascular reactivity and overall blood flow and pressure regulation, it has become increasingly clear that extracellular ATP also plays important regulatory roles in the vascular inflammatory response. Vascular inflammation can be characterized as acute (physiological) or chronic (pathological) in nature.The acute vascular inflammatory response is an innate process of inflammatory cell homing to infected or damaged tissues resulting from integrated cross-talk between circulating leukocytes and the vascular endothelium, primarily at the level of postcapillary venules [61]. This process has been highly studied and is now known to occur in a step-wise manner beginning with local recruitment, rolling (fast and slow), adhesion and final extravasation into the surrounding tissue (reviewed in [62...

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Histamine Induces ATP Release from Human Subcutaneous Fibroblasts, via Pannexin-1 Hemichannels, Leading to Ca2+ Mobilization and Cell Proliferation

Cited by 78 publications

References 57 publications

ATP release through pannexon channels

ATP release through pannexon channels

Peripheral and Spinal Mechanisms of Pain and Dry Needling Mediated Analgesia: A Clinical Resource Guide for Health Care Professionals

Function and Regulation of Pannexin 1 Channels in the Vascular Endothelium

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