β-Arrestin-2 Desensitizes the Transient Receptor Potential Vanilloid 1 (TRPV1) Channel

Por, Elaine D.; Bierbower, Sonya M.; Berg, Kelly A.; Gomez, Ruben; Akopian, Armen N.; Wetsel, William C.; Jeske, Nathaniel Aaron

doi:10.1074/jbc.m112.391847

Cited by 43 publications

(65 citation statements)

References 61 publications

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“…67,77,78 Recent research has demonstrated that β-arrestins are novel regulators that can regulate the function of several TRP channels and desensitize ionotropic receptors. 11,77,79 Por ED et al provided the first evidence that β-arrestin2 regulates TRPV1 receptor through its role as a scaffolding protein. 11 Regulation of TRPV1 by β-arrestin2 induces PKA phosphorylation and effectively desensitizes the ionotropic receptor, which is implicated in a variety of inflammatory and pain conditions.…”

Section: Mor Sensitizes Trpv1 Via β-Arrestin2mentioning

confidence: 98%

“…8,9 A prominent feature of opioid-induced hyperalgesia is enhanced responsiveness to noxious thermal stimulation, suggesting that transient receptor potential vanilloid type 1 (TRPV1) channels may be an important element of this response. 10 TRPV1 is a nonselective cation (Ca 2+ ) channel that is involved in a variety of nociceptive processes 11 and can be activated by multiple stimuli, including acidic pH (≤ 5.9), noxious heat (> 42°C), endocannabinoids, endogenous lipids, and capsaicin. [12][13][14][15] TRPV1 is widely distributed in the sensory terminals of central and peripheral neurons.…”

Section: Introductionmentioning

confidence: 99%

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The mechanism of μ-opioid receptor (MOR)-TRPV1 crosstalk in TRPV1 activation involves morphine anti-nociception, tolerance and dependence

et al. 2015

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Initiated by the activation of various nociceptors, pain is a reaction to specific stimulus modalities. The μ-opioid receptor (MOR) agonists, including morphine, remain the most potent analgesics to treat patients with moderate to severe pain. However, the utility of MOR agonists is limited by the adverse effects associated with the use of these drugs, including analgesic tolerance and physical dependence. A strong connection has been suggested between the expression of the transient receptor potential vanilloid type 1 (TRPV1) ion channel and the development of inflammatory hyperalgesia. TRPV1 is important for thermal nociception induction, and is mainly expressed on sensory neurons. Recent reports suggest that opioid or TRPV1 receptor agonist exposure has contrasting consequences for anti-nociception, tolerance and dependence. Chronic morphine exposure modulates TRPV1 activation and induces the anti-nociception effects of morphine. The regulation of many downstream targets of TRPV1 plays a critical role in this process, including calcitonin gene-related peptide (CGRP) and substance P (SP). Additional factors also include capsaicin treatment blocking the anti-nociception effects of morphine in rats, as well as opioid modulation of TRPV1 responses through the cAMP-dependent PKA pathway and MAPK signaling pathways. Here, we review new insights concerning the mechanism underlying MOR-TRPV1 crosstalk and signaling pathways and discuss the potential mechanisms of morphine-induced anti-nociception, tolerance and dependence associated with the TRPV1 signaling pathway and highlight how understanding these mechanisms might help find therapeutic targets for the treatment of morphine induced antinociception, tolerance and dependence.

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Section: Mor Sensitizes Trpv1 Via β-Arrestin2mentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

The mechanism of μ-opioid receptor (MOR)-TRPV1 crosstalk in TRPV1 activation involves morphine anti-nociception, tolerance and dependence

et al. 2015

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“…92 Additionally, β-arrestin scaffolding of ubiquitin modulates TRPV4 activation, 93 providing the first example of arrestin-scaffolded regulation of an ion channel. Although TRPV4 has little to do with sensory perception by primary afferent neurons, β-arrestin molecules were also found to target TRPV1 ion channels with scaffolding phosphodiesterase 4D5 (PDE4D5, 94 ). Similar scaffolding of PDE4 by β-arrestin effectively regulates cAMP recruitment following β-adrenergic receptor activation.…”

Section: β-Arrestinmentioning

confidence: 99%

Peripheral Scaffolding and Signaling Pathways in Inflammatory Pain

Jeske

2015

Progress in Molecular Biology and Translational Science

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“…In the latter case, a pool of another PDE4D isoform, PDE4D8, is actually released from the ² 1-AR to allow more extensive diffusion of cAMP following ² 1-AR activation. Localised PDE4D5 has also been shown to associate with the 5-hydroxytryptamine receptor [36] and the transient receptor vanilloid 1 (TRPV1) [37] to regulate downstream signalling. Over-expression of dominant negative PDE4D5 constructs increased release of glucagon-like peptide 1 (GLP-1) to influence insulin secretion in enteroendocrine L cells [38].…”

Section: Beta-arrestinmentioning

confidence: 99%

Location, location, location: PDE4D5 function is directed by its unique N-terminal region

Wills

Ehsan

Whiteley

et al. 2016

Cellular Signalling

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Compartmentalised cAMP SignallingCharacterisation of the cyclic AMP signalling pathway in glycogenolysis as the first "second messenger" system opened the door for study of "cellular signalling" as a Depending on receptor type, cAMP produced at the cell membrane can reach far into the cell or stay localised to its site of production. The distance cAMP travels and its ability to form three-dimensional gradients, triggering activation of cAMP effectors, are determined by the phosphodiesterase (PDE) landscape [8]. Often, PDEs are expressed at low levels yet it is their localisation to demarcated positions within cells that underpins both their effectiveness and function. Indeed, reporter technology devised to visualise cAMP gradient formation following specific receptor activation [9] has confirmed that PDE positioning is crucial to the formation of multiple, simultaneous and spatially distinct cAMP gradients that drive defined physiological responses. PDE familiesPDEs are a vast super-family of distinct, highly regulated enzymes which can be classified based on primary structure into class I, II and III -the largest, class I,

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β-Arrestin-2 Desensitizes the Transient Receptor Potential Vanilloid 1 (TRPV1) Channel

Cited by 43 publications

References 61 publications

The mechanism of μ-opioid receptor (MOR)-TRPV1 crosstalk in TRPV1 activation involves morphine anti-nociception, tolerance and dependence

The mechanism of μ-opioid receptor (MOR)-TRPV1 crosstalk in TRPV1 activation involves morphine anti-nociception, tolerance and dependence

Peripheral Scaffolding and Signaling Pathways in Inflammatory Pain

Location, location, location: PDE4D5 function is directed by its unique N-terminal region

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