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

2019 ◽  
Vol 7 (4) ◽  
pp. 62 ◽  
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.

scholarly journals Understanding diverse TRPV1 signaling – an update

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 1978
Author(s):  
Michael Andresen
Keyword(s):  
Sensory Neurons ◽  
Synaptic Vesicles ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
G Protein Coupled Receptors ◽  
Transient Receptor Potential Vanilloid ◽  
Discrete Population ◽  
Transient Receptor ◽  
G Protein Coupled ◽  
Central Terminal

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.

Transient receptor potential vanilloid 4 mediates protease activated receptor 2-induced sensitization of colonic afferent nerves and visceral hyperalgesia

2008 ◽  
Vol 294 (5) ◽  
pp. G1288-G1298 ◽  
Author(s):  
Walter E. B. Sipe ◽  
Stuart M. Brierley ◽  
Christopher M. Martin ◽  
Benjamin D. Phillis ◽  
Francisco Bautista Cruz ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Action Potentials ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Mechanical Hyperalgesia ◽  
Transient Receptor Potential Vanilloid ◽  
Afferent Neurons ◽  
Nociceptive Neurons ◽  
Afferent Fibers ◽  
Transient Receptor

Protease-activated receptor (PAR2) is expressed by nociceptive neurons and activated during inflammation by proteases from mast cells, the intestinal lumen, and the circulation. Agonists of PAR2 cause hyperexcitability of intestinal sensory neurons and hyperalgesia to distensive stimuli by unknown mechanisms. We evaluated the role of the transient receptor potential vanilloid 4 (TRPV4) in PAR2-induced mechanical hyperalgesia of the mouse colon. Colonic sensory neurons, identified by retrograde tracing, expressed immunoreactive TRPV4, PAR2, and calcitonin gene-related peptide and are thus implicated in nociception. To assess nociception, visceromotor responses (VMR) to colorectal distension (CRD) were measured by electromyography of abdominal muscles. In TRPV4+/+ mice, intraluminal PAR2 activating peptide (PAR2-AP) exacerbated VMR to graded CRD from 6–24 h, indicative of mechanical hyperalgesia. PAR2-induced hyperalgesia was not observed in TRPV4−/− mice. PAR2-AP evoked discharge of action potentials from colonic afferent neurons in TRPV4+/+ mice, but not from TRPV4−/− mice. The TRPV4 agonists 5′,6′-epoxyeicosatrienoic acid and 4α-phorbol 12,13-didecanoate stimulated discharge of action potentials in colonic afferent fibers and enhanced current responses recorded from retrogradely labeled colonic dorsal root ganglia neurons, confirming expression of functional TRPV4. PAR2-AP enhanced these responses, indicating sensitization of TRPV4. Thus TRPV4 is expressed by primary spinal afferent neurons innervating the colon. Activation of PAR2 increases currents in these neurons, evokes discharge of action potentials from colonic afferent fibers, and induces mechanical hyperalgesia. These responses require the presence of functional TRPV4. Therefore, TRPV4 is required for PAR2-induced mechanical hyperalgesia and excitation of colonic afferent neurons.

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

2019 ◽  
Vol 374 (1785) ◽  
pp. 20190291 ◽  
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’.

scholarly journals Transient Receptor Potential (TRP) and Thermoregulation in Animals: Structural Biology and Neurophysiological Aspects

Animals ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 106
Author(s):  
Karina Lezama-García ◽  
Daniel Mota-Rojas ◽  
Alfredo M. F. Pereira ◽  
Julio Martínez-Burnes ◽  
Marcelo Ghezzi ◽  
...  
Keyword(s):  
Thermal Stress ◽  
Structural Biology ◽  
Transient Receptor Potential ◽  
Transmembrane Proteins ◽  
Receptor Potential ◽  
G Protein Coupled Receptors ◽  
Cation Channels ◽  
Transient Receptor ◽  
Opening And Closing ◽  
G Protein Coupled

This review presents and analyzes recent scientific findings on the structure, physiology, and neurotransmission mechanisms of transient receptor potential (TRP) and their function in the thermoregulation of mammals. The aim is to better understand the functionality of these receptors and their role in maintaining the temperature of animals, or those susceptible to thermal stress. The majority of peripheral receptors are TRP cation channels formed from transmembrane proteins that function as transductors through changes in the membrane potential. TRP are classified into seven families and two groups. The data gathered for this review include controversial aspects because we do not fully know the mechanisms that operate the opening and closing of the TRP gates. Deductions, however, suggest the intervention of mechanisms related to G protein-coupled receptors, dephosphorylation, and ligands. Several questions emerge from the review as well. For example, the future uses of these data for controlling thermoregulatory disorders and the invitation to researchers to conduct more extensive studies to broaden our understanding of these mechanisms and achieve substantial advances in controlling fever, hyperthermia, and hypothermia.

What Evolutionary Evidence Implies About the Identity of the Mechanoelectrical Couplers in Vascular Smooth Muscle Cells

Physiology ◽  
2021 ◽  
Vol 36 (5) ◽  
pp. 292-306
Author(s):  
Heather A. Drummond
Keyword(s):  
Transient Receptor Potential ◽  
Molecular Model ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Potential Channels ◽  
Transient Receptor ◽  
Paradigm Shifting ◽  
G Protein Coupled ◽  
Evolutionary Role

Loss of pressure-induced vasoconstriction increases susceptibility to renal and cerebral vascular injury. Favored paradigms underlying initiation of the response include transient receptor potential channels coupled to G protein-coupled receptors or integrins as transducers. Degenerin channels may also mediate the response. This review addresses the 1) evolutionary role of these molecules in mechanosensing, 2) limitations to identifying mechanosensitive molecules, and 3) paradigm shifting molecular model for a VSMC mechanosensor.

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