scholarly journals Sumatriptan activates TRPA1

2019 ◽  
Vol 2 ◽  
pp. 251581631984715
Author(s):  
Alexandru Babes ◽  
Cristian Neacsu ◽  
Michael JM Fischer ◽  
Karl Messlinger
Keyword(s):  
Side Effects ◽  
Trigeminal Ganglion ◽  
Transient Receptor Potential ◽  
Animal Experiments ◽  
Receptor Potential ◽  
Membrane Currents ◽  
Nociceptive Neurons ◽  
Trigeminal Ganglion Neurons ◽  
Transient Receptor ◽  
Ganglion Neurons

Background: Migraine therapy with sumatriptan may cause adverse side effects like pain at the injection site, muscle pain, and transient aggravation of headaches. In animal experiments, sumatriptan excited or sensitized slowly conducting meningeal afferents. We hypothesized that sumatriptan may activate transduction channels of the “irritant receptor,” the transient receptor potential ankyrin type (TRPA1) expressed in nociceptive neurons. Methods: Calcium microfluorometry was performed in HEK293t cells transfected with human TRPA1 (hTRPA1) or a mutated channel (TRPA1-3C) and in dissociated trigeminal ganglion neurons. Membrane currents were recorded in the whole-cell patch clamp configuration. Results: Sumatriptan (10 and 400 µM) evoked calcium transients in hTRPA1-expressing HEK293t cells also activated by the TRPA1 agonist carvacrol (100 µM). In TRPA1-3C-expressing HEK293t cells, sumatriptan had hardly any effect. In rat trigeminal ganglion neurons, sumatriptan, carvacrol, and the transient receptor potential vanillod type 1 agonist capsaicin (1 µM) generated robust calcium signals. All sumatriptan-sensitive neurons (8% of the sample) were also activated by carvacrol (14%) and capsaicin (48%). In HEK293-hTRPA1 cells, sumatriptan (100 µM) evoked outwardly rectifying currents, which were almost completely inhibited by the TRPA1 antagonist HC-030031 (10 µM). Conclusion: Sumatriptan activates TRPA1 channels inducing calcium inflow and membrane currents. TRPA1-dependent activation of primary afferents may explain the painful side effects of sumatriptan.

scholarly journals Transient Receptor Potential Channels Encode Volatile Chemicals Sensed by Rat Trigeminal Ganglion Neurons

PLoS ONE ◽  
2013 ◽  
Vol 8 (10) ◽  
pp. e77998 ◽  
Author(s):  
Matthias Lübbert ◽  
Jessica Kyereme ◽  
Nicole Schöbel ◽  
Leopoldo Beltrán ◽  
Christian Horst Wetzel ◽  
...  
Keyword(s):  
Trigeminal Ganglion ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Volatile Chemicals ◽  
Trigeminal Ganglion Neurons ◽  
Potential Channels ◽  
Transient Receptor ◽  
Ganglion Neurons

scholarly journals Eugenol Inhibits K+ Currents in Trigeminal Ganglion Neurons

2007 ◽  
Vol 86 (9) ◽  
pp. 898-902 ◽  
Author(s):  
H.Y. Li ◽  
C.-K. Park ◽  
S.J. Jung ◽  
S.-Y. Choi ◽  
S.J. Lee ◽  
...  
Keyword(s):  
Trigeminal Ganglion ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Inhibitory Effects ◽  
Independent Manner ◽  
Voltage Gated ◽  
Trigeminal Ganglion Neurons ◽  
Transient Receptor ◽  
Ganglion Neurons

Eugenol, a natural capsaicin congener, is widely used in dentistry. Eugenol inhibits voltage-activated Na+ and Ca2+ channels in a transient receptor potential vanilloid 1 (TRPV1)-independent manner. We hypothesized that eugenol also inhibits voltage-gated K+ currents, and investigated this in rat trigeminal ganglion neurons and in a heterologous system using whole-cell patch clamping. Eugenol inhibited voltage-gated K+ currents, and the inhibitory effects of eugenol were observed in both capsaicin-sensitive and capsaicin-insensitive neurons. Pre-treatment with capsazepine, a well-known antagonist of TRPV1, failed to block the inhibitory effects of eugenol on K+ currents, suggesting no involvement of TRPV1. Eugenol inhibited human Kv1.5 currents stably expressed in Ltk− cells, where TRPV1 is not endogenously expressed. We conclude that eugenol inhibits voltage-gated K+ currents in a TRPV1-independent manner. The inhibition of voltage-gated K+ currents is likely to contribute to the irritable action of eugenol. Abbreviations: human Kv1.5 channel, hKv1.5; transient receptor potential vanilloid 1, TRPV1.

scholarly journals Molecular Basis of Cav2.3 Calcium Channels in Rat Nociceptive Neurons

2006 ◽  
Vol 282 (7) ◽  
pp. 4757-4764 ◽  
Author(s):  
Zhi Fang ◽  
Chul-Kyu Park ◽  
Hai Ying Li ◽  
Hyun Yeong Kim ◽  
Seong-Hae Park ◽  
...  
Keyword(s):  
Calcium Channels ◽  
Single Cell ◽  
Sensory Neurons ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Rt Pcr ◽  
Nociceptive Neurons ◽  
Transient Receptor ◽  
Ganglion Neurons

Cav2.3 calcium channels play an important role in pain transmission in peripheral sensory neurons. Six Cav2.3 isoforms resulting from different combinations of three inserts (inserts I and II in the II–III loop and insert III in the carboxyl-terminal region) have been identified in different mammalian tissues. To date, however, Cav2.3 isoforms unique to primary sensory neurons have not been identified. In this study, we determined Cav2.3 isoforms expressed in the rat trigeminal ganglion neurons. Whole tissue reverse transcription (RT)-PCR analyses revealed that only two isoforms, Cav2.3a and Cav2.3e, are present in TG neurons. Using single cell RT-PCR, we found that Cav2.3e is the major isoform, whereas Cav2.3e expression is highly restricted to small (<16 μm) isolectin B4-negative and tyrosine kinase A-positive neurons. Cav2.3e was also preferentially detected in neurons expressing the nociceptive marker, transient receptor potential vanilloid 1. Single cell RT-PCR following calcium imaging and whole-cell patch clamp recordings provided evidence of an association between an R-type calcium channel component and Cav2.3e expression. Our results suggest that Cav2.3e in sensory neurons may be a potential target for the treatment of pain.

scholarly journals Vasopressin at Central Levels and Consequences of Dehydration

2016 ◽  
Vol 68 (Suppl. 2) ◽  
pp. 19-23 ◽  
Author(s):  
Daniel G. Bichet
Keyword(s):  
Animal Studies ◽  
Transient Receptor Potential ◽  
Animal Experiments ◽  
Extracellular Fluid ◽  
Receptor Potential ◽  
Circumventricular Organ ◽  
Thermal Perception ◽  
Trpv1 Channel ◽  
Vasopressin Release ◽  
Transient Receptor

Disorders of water balance are a common feature of clinical practice. An understanding of the physiology and pathophysiology of central vasopressin release and perception of thirst is the key to diagnosis and management of these disorders. Mammals are osmoregulators; they have evolved mechanisms that maintain extracellular fluid osmolality near a stable value, and, in animal studies, osmoregulatory neurons express a truncated delta-N variant of the transient receptor potential vannilloid (TRPV1) channel involved in hypertonicity and thermal perception while systemic hypotonicity might be perceived by TRPV4 channels. Recent cellular and optogenetic animal experiments demonstrate that, in addition to the multifactorial process of excretion, circumventricular organ sensors reacting to osmotic pressure and angiotensin II, subserve genesis of thirst, volume regulation and behavioral effects of thirst avoidance.

Electroacupuncture reduces fibromyalgia pain by downregulating the TRPV1–pERK signalling pathway in the mouse brain

2020 ◽  
Vol 38 (2) ◽  
pp. 101-108 ◽  
Author(s):  
Hsin-Cheng Hsu ◽  
Ching-Liang Hsieh ◽  
Kun-Ta Lee ◽  
Yi-Wen Lin
Keyword(s):  
Side Effects ◽  
Pain Relief ◽  
Mouse Brain ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Signalling Pathway ◽  
World Health ◽  
Transient Receptor ◽  
Health Organization ◽  
Psychological Origin

Background: Acupuncture has been clinically recommended as a method of pain relief by the World Health Organization and is widely used by medical doctors. Fibromyalgia (FM) pain has a complex physiological and psychological origin and can be pharmacologically treated with duloxetine, milnacipran and pregabalin. However, these drugs produce undesirable side effects, such as headaches, nausea and diarrhoea. Acupuncture may serve as an effective alternative treatment for pain relief with few side effects. Aims: We hypothesised that acupuncture would reduce FM pain by influencing transient receptor potential cation channel subfamily V member 1 (TRPV1) and the downstream phosphorylated extracellular signal-regulated kinases (pERK), which are located in the central thalamus, amygdala and cortex. Methods: A FM mouse model was established by injecting two doses of acid saline into 32 female C57/B6 mice. The mice were then assigned to different subgroups (n=8 each) and treated with electroacupuncture (EA) or EA sham control. TRPV1 and pERK expression levels were measured using Western blotting and immunohistochemistry. Results: Our results demonstrated that the expression of TRPV1 and pERK in the thalamus, amygdala and somatosensory cortex was normal in the control mice, but significantly increased in FM mice; these FM-induced changes in expression were attenuated by EA. Conclusion: Our data suggest that EA can reverse the central sensitisation of the TRPV1-ERK signalling pathway in the mouse brain. Thus, our findings provide mechanistic evidence supporting the potential therapeutic efficacy of EA for treating FM pain.

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