scholarly journals A Systematical Survey on the TRP Channels Provides New Insight into Its Functional Diversity in Zhikong Scallop (Chlamys farreri)

2021 ◽  
Vol 22 (20) ◽  
pp. 11075
Author(s):  
Cheng Peng ◽  
Zujing Yang ◽  
Zhi Liu ◽  
Shenhai Wang ◽  
Haitao Yu ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Developmental Stages ◽  
Trp Channels ◽  
Light Transmission ◽  
Receptor Potential ◽  
Structural Features ◽  
High Temperature Stress ◽  
Chlamys Farreri ◽  
Zhikong Scallop ◽  
Sense And Respond

Transient receptor potential (TRP) channel plays a significant role in mediating various sensory physiological functions. It is widely present in the vertebrate and invertebrate genomes and can be activated by multiple compounds, messenger molecules, temperature, and mechanical stimulation. Mollusks are the second largest phylum of the animal kingdom and are sensitive to environmental factors. However, the molecular underpinnings through which mollusks sense and respond to environmental stimulus are unknown. In this study, we systematically identified and characterized 17 TRP channels (C.FA TRPs, seven subfamilies) in the genome of the Zhikong scallop (Chlamys farreri). All C.FA TRPs had six transmembrane structures (TM1–TM6). The sequences and structural features of C.FA TRPs are highly conserved with TRP channels of other species. Spatiotemporal expression profiling suggested that some C.FA TRPs participated in the early embryonic development of scallops and the sensory process of adult tissues. Notably, the expression of C.FA TRPM3 continuously increased during developmental stages and was highest among all C.FA TRPs. C.FA TRPC-α was specifically expressed in eyes, which may be involved in light transmission of scallop eyes. Under high temperature stress, C.FA TRPA1 and C.FA TRPA1-holomog upregulated significantly, which indicated that the TRPA subfamily is the thermoTRPs channel of scallops. Our results provided the first systematic study of TRP channels in scallops, and the findings will provide a valuable resource for a better understanding of TRP evolution and function in mollusks.

scholarly journals Cryo-EM structure of the receptor-activated TRPC5 ion channel at 2.9 angstrom resolution

2018 ◽  
Author(s):  
Jingjing Duan ◽  
Jian Li ◽  
Gui-Lan Chen ◽  
Bo Zeng ◽  
Kechen Xie ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Structural Features ◽  
Cation Binding ◽  
Activation Mechanism ◽  
Cation Binding Site ◽  
Resolution Electron ◽  
The Central Nervous System ◽  
Transient Receptor

AbstractThe transient receptor potential canonical subfamily member 5 (TRPC5) is a non-selective calcium-permeant cation channel. As a depolarizing channel, its function is studied in the central nervous system and kidney. TRPC5 forms heteromultimers with TRPC1, but also forms homomultimers. It can be activated by reducing agents through reduction of the extracellular disulfide bond. Here we present the 2.9 Å resolution electron cryo-microscopy (cryo-EM) structure of TRPC5. The structure of TRPC5 in its apo state is partially open, which may be related to the weak activation of TRPC5 in response to extracellular pH. We also report the conserved negatively charged residues of the cation binding site located in the hydrophilic pocket between S2 and S3. Comparison of the TRPC5 structure to previously determined structures of other TRPC and TRP channels reveals differences in the extracellular pore domain and in the length of the S3 helix. Together, these results shed light on the structural features that contribute to the specific activation mechanism of the receptor-activated TRPC5.

scholarly journals Computational Modeling to Explain Why 5,5-Diarylpentadienamides are TRPV1 Antagonists

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1765
Author(s):  
Julio Caballero
Keyword(s):  
Transient Receptor Potential ◽  
Structural Information ◽  
Chemical Activation ◽  
Receptor Potential ◽  
Quantitative Structure Activity Relationship ◽  
Structural Features ◽  
Transient Receptor Potential Vanilloid ◽  
Protein Residues ◽  
Topological Features ◽  
Transient Receptor

Several years ago, the crystallographic structures of the transient receptor potential vanilloid 1 (TRPV1) in the presence of agonists and antagonists were reported, providing structural information about its chemical activation and inactivation. TRPV1’s activation increases the transport of calcium and sodium ions, leading to the excitation of sensory neurons and the perception of pain. On the other hand, its antagonistic inactivation has been explored to design analgesic drugs. The interactions between the antagonists 5,5-diarylpentadienamides (DPDAs) and TRPV1 were studied here to explain why they inactivate TRPV1. The present work identified the structural features of TRPV1–DPDA complexes, starting with a consideration of the orientations of the ligands inside the TRPV1 binding site by using molecular docking. After this, a chemometrics analysis was performed (i) to compare the orientations of the antagonists (by using LigRMSD), (ii) to describe the recurrent interactions between the protein residues and ligand groups in the complexes (by using interaction fingerprints), and (iii) to describe the relationship between topological features of the ligands and their differential antagonistic activities (by using a quantitative structure–activity relationship (QSAR) with 2D autocorrelation descriptors). The interactions between the DPDA groups and the residues Y511, S512, T550, R557, and E570 (with a recognized role in the binding of classic ligands), and the occupancy of isoquinoline or 3-hydroxy-3,4-dihydroquinolin-2(1H)-one groups of the DPDAs in the vanilloid pocket of TRPV1 were clearly described. Based on the results, the structural features that explain why DPDAs inactivate TRPV1 were clearly exposed. These features can be considered for the design of novel TRPV1 antagonists.

Intragastric administration of capsiate, a transient receptor potential channel agonist, triggers thermogenic sympathetic responses

2011 ◽  
Vol 110 (3) ◽  
pp. 789-798 ◽  
Author(s):  
Kaori Ono ◽  
Masako Tsukamoto-Yasui ◽  
Yoshiko Hara-Kimura ◽  
Naohiko Inoue ◽  
Yoshihito Nogusa ◽  
...  
Keyword(s):  
Sympathetic Nerve ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Low Frequency ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
Intragastric Administration ◽  
Brown Adipose ◽  
Reflex Arc ◽  
Transient Receptor

The sympathetic thermoregulatory system controls the magnitude of adaptive thermogenesis in correspondence with the environmental temperature or the state of energy intake and plays a key role in determining the resultant energy storage. However, the nature of the trigger initiating this reflex arc remains to be determined. Here, using capsiate, a digestion-vulnerable capsaicin analog, we examined the involvement of specific activation of transient receptor potential (TRP) channels within the gastrointestinal tract in the thermogenic sympathetic system by measuring the efferent activity of the postganglionic sympathetic nerve innervating brown adipose tissue (BAT) in anesthetized rats. Intragastric administration of capsiate resulted in a time- and dose-dependent increase in integrated BAT sympathetic nerve activity (SNA) over 180 min, which was characterized by an emergence of sporadic high-activity phases composed of low-frequency bursts. This increase in BAT SNA was abolished by blockade of TRP channels as well as of sympathetic ganglionic transmission and was inhibited by ablation of the gastrointestinal vagus nerve. The activation of SNA was delimited to BAT and did not occur in the heart or pancreas. These results point to a neural pathway enabling the selective activation of the central network regulating the BAT SNA in response to a specific stimulation of gastrointestinal TRP channels and offer important implications for understanding the dietary-dependent regulation of energy metabolism and control of obesity.

scholarly journals Characterization Of Selective TRPM8 Ligands And Their Structure Activity Response (S.A.R) Relationship

2010 ◽  
Vol 13 (2) ◽  
pp. 242 ◽  
Author(s):  
Muhammad Azhar Sherkheli ◽  
Angela K. Vogt-Eisele ◽  
Daniel Bura ◽  
Leopoldo R. Beltrán Márques ◽  
Günter Gisselmann ◽  
...  
Keyword(s):  
Ion Channels ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Parent Compound ◽  
Receptor Potential ◽  
Basic Research ◽  
Fold Increase ◽  
Ring Structure ◽  
Sensory Nerves ◽  
Transient Receptor Potential Melastatin

PURPOSE: Transient receptor potential melastatin-8 (TRPM8) is an ion channel expressed extensively in sensory nerves, human prostate and overexpressed in a variety of cancers including prostate, breast, lung, colon and skin melanomas. It is activated by innoxious cooling and chemical stimuli. TRPM8 activation by cooling or chemical agonists is reported to induce profound analgesia in neuropathic pain conditions. Known TRPM8 agonists like menthol and icilin cross-activate other thermo-TRP channels like TRPV3 and TRPA1 and mutually inhibit TRPM8. This limits the usefulness of menthol and icilin as TRPM8 ligands. Consequently, the identification of selective and potent ligands for TRPM8 is of high relevance both in basic research and for therapeutic applications. In the present investigation, a group of menthol derivates was characterized. These ligands are selective and potent agonists of TRPM8. Interestingly they do not activate other thermo-TRPs like TRPA1, TRPV1, TRPV2, TRPV3 and TRPV4. These ion channels are also nociceptors and target of many inflammatory mediators. METHODS: Investigations were performed in a recombinant system: Xenopus oocytes microinjected with cRNA of gene of interest were superfused with the test substances after initial responses of known standard agonists. Evoked currents were measured by two-electrode voltage clamp technique. RESULTS: The newly characterized ligands possess an up to six-fold higher potency (EC50 in low µM) and an up to two-fold increase in efficacy compared to the parent compound menthol. In addition, it is found that chemical derivatives of menthol like CPS-368, CPS-369, CPS-125, WS-5 and WS-12 are the most selective ligands for TRPM8. The enhanced activity and selectivity seems to be conferred by hexacyclic ring structure present in all ligands as substances like WS-23 which lack this functional group activate TRPM8 with much lower potency (EC50 in mM) and those with pentacyclcic ring structure (furanone compounds) are totally inactive. CONCLUSION: The new substances activate TRPM8 with a higher potency, efficacy and specificity than menthol and will thus be of importance for the development of pharmacological agents suitable for treatment and diagnosis of certain cancers and as analgesics. STATEMENT OF NOVELTY: The new compounds have an unmatched specificity for TRPM8 ion channels with additional display of high potency and efficacy. Thus these substances are better pharmacological tools for TRPM8 characterization then known compounds and it is suggested that these menthol-derivates may serve as model substances for the development of TRPM8 ligands.

scholarly journals Differential role of TRP channels in prostate cancer

2007 ◽  
Vol 35 (1) ◽  
pp. 133-135 ◽  
Author(s):  
N. Prevarskaya ◽  
M. Flourakis ◽  
G. Bidaux ◽  
S. Thebault ◽  
R. Skryma
Keyword(s):  
Prostate Cancer ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Clinical Problem ◽  
Tissue Growth ◽  
Transient Receptor Potential Channels ◽  
Potential Channels ◽  
Differentiation And Proliferation

A major clinical problem with PC (prostate cancer) is the cell's ability to survive and proliferate upon androgen withdrawal. Indeed, deregulated cell differentiation and proliferation, together with the suppression of apoptosis, provides the condition for abnormal tissue growth. Here, we examine the differential role of TRP (transient receptor potential) channels in the control of Ca2+ homoeostasis and growth of PC cells.

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