Membrane depolarization combined with Gq-activated G-protein-coupled receptors induce transient receptor potential channel 1 (TRPC1)- dependent potentiation of catecholamine release

The transient receptor potential vanilloid 1 (TRPV1) is densely expressed in spinal sensory neurons as well as in cranial sensory neurons, including their central terminal endings. Recent work in the less familiar cranial sensory neurons, despite their many similarities with spinal sensory neurons, suggest that TRPV1 acts as a calcium channel to release a discrete population of synaptic vesicles. The modular and independent regulation of release offers new questions about nanodomain organization of release and selective actions of G protein–coupled receptors.

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TRPA1 Channel is Involved in SLIGRL-Evoked Thermal and Mechanical Hyperalgesia in Mice

Medical Sciences ◽

10.3390/medsci7040062 ◽

2019 ◽

Vol 7 (4) ◽

pp. 62 ◽

Cited By ~ 1

Author(s):

Tsagareli ◽

Nozadze ◽

Tsiklauri ◽

Gurtskaia

Keyword(s):

Sensory Neurons ◽

Time Course ◽

Transient Receptor Potential ◽

Receptor Potential ◽

G Protein Coupled Receptors ◽

Mechanical Hyperalgesia ◽

Transient Receptor ◽

Mechanical Thresholds ◽

G Protein Coupled

Persistent itch (pruritus) accompanying dermatologic and systemic diseases can significantly impair the quality of life. It is well known that itch is broadly categorized as histaminergic (sensitive to antihistamine medications) or non-histaminergic. Sensory neurons expressing Mas-related G-protein-coupled receptors (Mrgprs) mediate histamine-independent itch. These receptors have been shown to bind selective pruritogens in the periphery and mediate non-histaminergic itch. For example, mouse MrgprA3 responds to chloroquine (an anti-malarial drug), and are responsible for relaying chloroquine-induced scratching in mice. Mouse MrgprC11 responds to a different subset of pruritogens including bovine adrenal medulla peptide (BAM8–22) and the peptide Ser-Leu-Ile-Gly-Arg-Leu (SLIGRL). On the other hand, the possibility that itch mediators also influence pain is supported by recent findings that most non-histaminergic itch mediators require the transient receptor potential ankyrin 1 (TRPA1) channel. We have recently found a significant increase of thermal and mechanical hyperalgesia induced by non-histaminergic pruritogens chloroquine and BAM8–22, injected into mice hindpaw, for the first 30–45 min. Pretreatment with TRPA1 channel antagonist HC-030031 did significantly reduce the magnitude of this hyperalgesia, as well as significantly shortened the time-course of hyperalgesia induced by chloroquine and BAM8–22. Here, we report that MrgprC11-mediated itch by their agonist SLIGRL is accompanied by heat and mechanical hyperalgesia via the TRPA1 channel. We measured nociceptive thermal paw withdrawal latencies and mechanical thresholds bilaterally in mice at various time points following intra-plantar injection of SLIGRL producing hyperalgesia. When pretreated with the TRPA1 antagonist HC-030031, we found a significant reduction of thermal and mechanical hyperalgesia.

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Evolution of acid nociception: ion channels and receptors for detecting acid

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2019.0291 ◽

2019 ◽

Vol 374 (1785) ◽

pp. 20190291 ◽

Cited By ~ 16

Author(s):

Luke A. Pattison ◽

Gerard Callejo ◽

Ewan St John Smith

Keyword(s):

Ion Channels ◽

Transient Receptor Potential ◽

Receptor Potential ◽

G Protein Coupled Receptors ◽

Transient Receptor Potential Vanilloid ◽

Ionic Homeostasis ◽

Acid Sensing Ion Channels ◽

Transient Receptor ◽

G Protein Coupled ◽

Cold Pressure

Nociceptors, i.e. sensory neurons tuned to detect noxious stimuli, are found in numerous phyla of the Animalia kingdom and are often polymodal, responding to a variety of stimuli, e.g. heat, cold, pressure and chemicals, such as acid. Owing to the ability of protons to have a profound effect on ionic homeostasis and damage macromolecular structures, it is no wonder that the ability to detect acid is conserved across many species. To detect changes in pH, nociceptors are equipped with an assortment of different acid sensors, some of which can detect mild changes in pH, such as the acid-sensing ion channels, proton-sensing G protein-coupled receptors and several two-pore potassium channels, whereas others, such as the transient receptor potential vanilloid 1 ion channel, require larger shifts in pH. This review will discuss the evolution of acid sensation and the different mechanisms by which nociceptors can detect acid. This article is part of the Theo Murphy meeting issue ‘Evolution of mechanisms and behaviour important for pain’.

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TRPV1 is a physiological regulator of μ-opioid receptors

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1717005114 ◽

2017 ◽

Vol 114 (51) ◽

pp. 13561-13566 ◽

Cited By ~ 18

Author(s):

Paul C. Scherer ◽

Nicholas W. Zaccor ◽

Neil M. Neumann ◽

Chirag Vasavda ◽

Roxanne Barrow ◽

...

Keyword(s):

G Protein ◽

Transient Receptor Potential ◽

Calcium Influx ◽

Receptor Potential ◽

Transient Receptor Potential Channel ◽

G Protein Signaling ◽

Protein Signaling ◽

Calcium Calmodulin Dependent ◽

Potential Strategy ◽

Transient Receptor

Opioids are powerful analgesics, but also carry significant side effects and abuse potential. Here we describe a modulator of the μ-opioid receptor (MOR1), the transient receptor potential channel subfamily vanilloid member 1 (TRPV1). We show that TRPV1 binds MOR1 and blocks opioid-dependent phosphorylation of MOR1 while leaving G protein signaling intact. Phosphorylation of MOR1 initiates recruitment and activation of the β-arrestin pathway, which is responsible for numerous opioid-induced adverse effects, including the development of tolerance and respiratory depression. Phosphorylation stands in contrast to G protein signaling, which is responsible for the analgesic effect of opioids. Calcium influx through TRPV1 causes a calcium/calmodulin-dependent translocation of G protein-coupled receptor kinase 5 (GRK5) away from the plasma membrane, thereby blocking its ability to phosphorylate MOR1. Using TRPV1 to block phosphorylation of MOR1 without affecting G protein signaling is a potential strategy to improve the therapeutic profile of opioids.

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