scholarly journals N-Arachidonoyl-l-Serine is Neuroprotective after Traumatic Brain Injury by Reducing Apoptosis

2011 ◽  
Vol 31 (8) ◽  
pp. 1768-1777 ◽  
Author(s):  
Ayelet Cohen-Yeshurun ◽  
Victoria Trembovler ◽  
Alexander Alexandrovich ◽  
Erik Ryberg ◽  
Peter J Greasley ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Specific Binding ◽  
Closed Head Injury ◽  
Receptor Potential ◽  
Bk Channels ◽  
Transient Receptor Potential Vanilloid ◽  
Lesion Volume ◽  
Protective Effects ◽  
Neuroprotective Effects ◽  
Trpv1 Channels

N-arachidonoyl-L-serine (AraS) is a brain component structurally related to the endocannabinoid family. We investigated the neuroprotective effects of AraS following closed head injury induced by weight drop onto the exposed fronto-parietal skull and the mechanisms involved. A single injection of AraS following injury led to a significant improvement in functional outcome, and to reduced edema and lesion volume compared with vehicle. Specific antagonists to CB2 receptors, transient receptor potential vanilloid 1 (TRPV1) or large conductance calcium-activated potassium (BK) channels reversed these effects. Specific binding assays did not indicate binding of AraS to the GPR55 cannabinoid receptor. N-arachidonoyl-l-serine blocked the attenuation in phosphorylated extracellular-signal-regulated kinase 1/2 (ERK) levels and led to an increase in pAkt in both the ipsilateral and contralateral cortices. Increased levels of the prosurvival factor Bcl-xL were evident 24 hours after injury in AraS-treated mice, followed by a 30% reduction in caspase-3 activity, measured 3 days after injury. Treatment with a CB2 antagonist, but not with a CB1 antagonist, reversed this effect. Our results suggest that administration of AraS leads to neuroprotection via ERK and Akt phosphorylation and induction of their downstream antiapoptotic pathways. These protective effects are related mostly to indirect signaling via the CB2R and TRPV1 channels but not through CB1 or GPR55 receptors.

scholarly journals Interactions between Chemesthesis and Taste: Role of TRPA1 and TRPV1

2021 ◽  
Vol 22 (7) ◽  
pp. 3360
Author(s):  
Mee-Ra Rhyu ◽  
Yiseul Kim ◽  
Vijay Lyall
Keyword(s):  
Transient Receptor Potential ◽  
Taste Receptor ◽  
Sensory Nerve ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Trpv1 Channels ◽  
Trigeminal Neurons ◽  
Calcitonin Gene ◽  
Transient Receptor

In addition to the sense of taste and olfaction, chemesthesis, the sensation of irritation, pungency, cooling, warmth, or burning elicited by spices and herbs, plays a central role in food consumption. Many plant-derived molecules demonstrate their chemesthetic properties via the opening of transient receptor potential ankyrin 1 (TRPA1) and transient receptor potential vanilloid 1 (TRPV1) channels. TRPA1 and TRPV1 are structurally related thermosensitive cation channels and are often co-expressed in sensory nerve endings. TRPA1 and TRPV1 can also indirectly influence some, but not all, primary taste qualities via the release of substance P and calcitonin gene-related peptide (CGRP) from trigeminal neurons and their subsequent effects on CGRP receptor expressed in Type III taste receptor cells. Here, we will review the effect of some chemesthetic agonists of TRPA1 and TRPV1 and their influence on bitter, sour, and salt taste qualities.

scholarly journals TRPV1 channels and the progesterone receptor Sig-1R interact to regulate pain

2018 ◽  
Vol 115 (7) ◽  
pp. E1657-E1666 ◽  
Author(s):  
Miguel Ortíz-Rentería ◽  
Rebeca Juárez-Contreras ◽  
Ricardo González-Ramírez ◽  
León D. Islas ◽  
Félix Sierra-Ramírez ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Sigma 1 Receptor ◽  
Trpv1 Channels ◽  
Nociceptive Responses ◽  
Sigma 1 ◽  
Transient Receptor ◽  
Thermal Stimuli

The Transient Receptor Potential Vanilloid 1 (TRPV1) ion channel is expressed in nociceptors where, when activated by chemical or thermal stimuli, it functions as an important transducer of painful and itch-related stimuli. Although the interaction of TRPV1 with proteins that regulate its function has been previously explored, their modulation by chaperones has not been elucidated, as is the case for other mammalian TRP channels. Here we show that TRPV1 physically interacts with the Sigma 1 Receptor (Sig-1R), a chaperone that binds progesterone, an antagonist of Sig-1R and an important neurosteroid associated to the modulation of pain. Antagonism of Sig-1R by progesterone results in the down-regulation of TRPV1 expression in the plasma membrane of sensory neurons and, consequently, a decrease in capsaicin-induced nociceptive responses. This is observed both in males treated with a synthetic antagonist of Sig-1R and in pregnant females where progesterone levels are elevated. This constitutes a previously undescribed mechanism by which TRPV1-dependent nociception and pain can be regulated.

scholarly journals Activation of TRPV1 channels leads to stimulation of NKCC1 cotransport in the lens

2018 ◽  
Vol 315 (6) ◽  
pp. C793-C802 ◽  
Author(s):  
Mohammad Shahidullah ◽  
Amritlal Mandal ◽  
Nicholas A. Delamere
Keyword(s):  
Ion Transport ◽  
Transient Receptor Potential ◽  
Ion Homeostasis ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Signaling Mechanism ◽  
Trpv1 Channels ◽  
Trpv1 Antagonist ◽  
Transient Receptor ◽  
Stimulation Of

Lens ion homeostasis is crucial in maintaining water content and, in turn, refractive index and transparency of the multicellular syncytium-like structure. New information is emerging on the regulation of ion transport in the lens by mechanisms that rely on transient receptor potential vanilloid (TRPV) ion channels. We found recently that TRPV1 activation leads to Ca2+/PKC-dependent ERK1/2 signaling. Here, we show that the TRPV1 agonist capsaicin (100 nM) and hyperosmotic solution (350 vs. 300 mosM) each caused an increase of bumetanide-inhibitable Rb uptake by intact porcine lenses and Na-K-2Cl cotransporter 1 (NKCC1) phosphorylation in the lens epithelium. The TRPV1 antagonist A889425 (1 µM) abolished the increases of Rb uptake and NKCC1 phosphorylation in response to hyperosmotic solution. Exposing lenses to hyperosmotic solution in the presence of MEK/ERK inhibitor U0126 (10 µM) or the with-no-lysine kinase (WNK) inhibitor WNK463 (1 µM) also prevented NKCC1 phosphorylation and the Rb uptake responses to hyperosmotic solution. WNK463 did not prevent the increase in ERK1/2 phosphorylation that occurs in response to capsaicin or hyperosmotic solution, suggesting that ERK1/2 activation occurs before WNK activation in the sequence of signaling events. Taken together, the evidence indicates that activation of TRPV1 is a critical early step in a signaling mechanism that responds to a hyperosmotic stimulus, possibly lens shrinkage. By activating ERK1/2 and WNK, TRPV1 activation leads to NKCC1 phosphorylation and stimulation of NKCC1-mediated ion transport.

Roles of Cannabidiol in the treatment and prevention of Alzheimer’s disease by multi-target actions

2021 ◽  
Vol 21 ◽  
Author(s):  
Xiao- Bei Zhang ◽  
Jintao Li ◽  
Juanhua Gu ◽  
Yue-Qin Zeng
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transient Receptor Potential ◽  
Senile Plaques ◽  
Memory Loss ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Peroxisome Proliferator ◽  
Protective Effects ◽  
Peroxisome Proliferator Activated Receptor

: Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases with chronic, progressive, and irreversible characteristics, affecting nearly 50 million older adults worldwide. The pathogenesis of AD includes the formation of senile plaques, the abnormal aggregation of tau protein and the gradual degeneration and death of cerebral cortical cells. The main symptoms are memory loss, cognitive decline and behavioral disorders. Studies indicate that cannabidiol(CBD) possesses various pharmacological activities including anti-inflammatory, anti-oxidation and neuroprotective activities. It has been suggested as a potential multi-target medicine for treatment of AD. In this review, we aim to summarize the underlying mechanisms and protective effects of CBD on signaling pathways and central receptors involved in the pathogenesis of AD, including the endocannabinoid system（eCBs）, the Transient receptor potential vanilloid type 1(TRPV1) receptor, and the Peroxisome proliferator-activated receptor (PPAR) receptor.

scholarly journals Pore Helix Domain Is Critical to Camphor Sensitivity of Transient Receptor Potential Vanilloid 1 Channel

2012 ◽  
Vol 116 (4) ◽  
pp. 903-917 ◽  
Author(s):  
Lenka Marsakova ◽  
Filip Touska ◽  
Jan Krusek ◽  
Viktorie Vlachova
Keyword(s):  
Spatial Distribution ◽  
Plasma Membranes ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Structural Basis ◽  
Transient Receptor Potential Vanilloid ◽  
Trpv1 Channel ◽  
Patch Clamp Technique ◽  
Trpv1 Channels ◽  
Transient Receptor

Background The recent discovery that camphor activates and strongly desensitizes the capsaicin-sensitive and noxious heat-sensitive channel transient receptor potential vanilloid subfamily member 1 (TRPV1) has provided new insights and opened up new research paths toward understanding why this naturally occurring monoterpene is widely used in human medicine for its local counter-irritant, antipruritic, and anesthetic properties. However, the molecular basis for camphor sensitivity remains mostly unknown. The authors attempt to explore the nature of the activation pathways evoked by camphor and narrow down a putative interaction site at TRPV1. Methods The authors transiently expressed wild-type or specifically mutated recombinant TRPV1 channels in human embryonic kidney cells HEK293T and recorded cation currents with the whole cell, patch clamp technique. To monitor changes in the spatial distribution of phosphatidylinositol 4,5-bisphosphate, they used fluorescence resonance energy transfer measurements from cells transfected with the fluorescent protein-tagged pleckstrin homology domains of phospholipase C. Results The results revealed that camphor modulates TRPV1 channel through the outer pore helix domain by affecting its overall gating equilibrium. In addition, camphor, which generally is known to decrease the fluidity of cell plasma membranes, may also regulate the activity of TRPV1 by inducing changes in the spatial distribution of phosphatidylinositol-4,5-bisphosphate on the inner leaflet of the plasma membrane. Conclusions The findings of this study provide novel insights into the structural basis for the modulation of TRPV1 channel by camphor and may provide an explanation for the mechanism by which camphor modulates thermal sensation in vivo.

scholarly journals Capsaicin-Sensitive Sensory Nerves and the TRPV1 Ion Channel in Cardiac Physiology and Pathologies

2020 ◽  
Vol 21 (12) ◽  
pp. 4472
Author(s):  
Tamara Szabados ◽  
Kamilla Gömöri ◽  
Laura Pálvölgyi ◽  
Anikó Görbe ◽  
István Baczkó ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ion Channel ◽  
Transient Receptor Potential ◽  
Heart Diseases ◽  
Receptor Potential ◽  
Cell Types ◽  
Sensory Nerves ◽  
Transient Receptor Potential Vanilloid ◽  
Cardiac Diseases ◽  
Trpv1 Channels

Cardiovascular diseases, including coronary artery disease, ischemic heart diseases such as acute myocardial infarction and postischemic heart failure, heart failure of other etiologies, and cardiac arrhythmias, belong to the leading causes of death. Activation of capsaicin-sensitive sensory nerves by the transient receptor potential vanilloid 1 (TRPV1) capsaicin receptor and other receptors, as well as neuropeptide mediators released from them upon stimulation, play important physiological regulatory roles. Capsaicin-sensitive sensory nerves also contribute to the development and progression of some cardiac diseases, as well as to mechanisms of endogenous stress adaptation leading to cardioprotection. In this review, we summarize the role of capsaicin-sensitive afferents and the TRPV1 ion channel in physiological and pathophysiological functions of the heart based mainly on experimental results and show their diagnostic or therapeutic potentials. Although the actions of several other channels or receptors expressed on cardiac sensory afferents and the effects of TRPV1 channel activation on different non-neural cell types in the heart are not precisely known, most data suggest that stimulation of the TRPV1-expressing sensory nerves or stimulation/overexpression of TRPV1 channels have beneficial effects in cardiac diseases.

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