scholarly journals The Cutting Edge Research of Functional Gastrointestinal Disorders in Japan: Review on JGA Core Symposium 2018–2020

Digestion ◽  
2020 ◽  
pp. 1-6
Author(s):  
Toshiro Sugiyama ◽  
Akiko Shiotani
Keyword(s):  
Ion Channel ◽  
Life Stress ◽  
Molecular Mechanisms ◽  
Transient Receptor Potential ◽  
Maternal Separation ◽  
Functional Gastrointestinal Disorders ◽  
Receptor Potential ◽  
Nerve Endings ◽  
Transient Receptor Potential Vanilloid ◽  
Α Diversity

Highly impacted articles on functional gastrointestinal (GI) disorders research presented at the core symposium held in the Japanese Gastroenterological Association (JGA) annual meeting 2018–2020 are selected and summarized. Regarding visceral hypersensitivity and sensor in GI tracts, transient receptor potential vanilloid 4 ion channel and acid-sensitive ion channel were candidates for hypersensitivity in GI tracts. ATP release from vesicular nucleotide transporter may be a key pathway to sensitize the nerve endings. Regarding inflammation and mucosal immune responses, patients infected with <i>H. pylori</i> having Ser70 type single nucleotide polymorphism of NapA gene was associated with <i>H. pylor</i>i-related dyspepsia via gastric dysmotility. Gastric histology infected with Ser70 type NapA was shown severe infiltration of neutrophils into intramuscular layer. Macrophages, mast cells, and neutrophils are infiltrated in the colon of irritable bowel syndrome (IBS) patients and the locally produced IL-1β upregulated brain-derived neurotrophic factor (BDNF) in enteric glia cells. BDNF can also stimulate nerve endings and might be linked to pain in the colon. Dysbiosis in the composition of commensal bacteria communities is associated with the pathogenesis of various diseases including IBS and gut-brain interaction. The investigation on the mucosa-associated microbiota (MAM) is essential for understanding the interactions. The α-diversity and β-diversity of MAM indices are significantly different among IBS-D, IBS-C, and controls, and the different diversity might contribute to the pathophysiology of IBS. As research works on psychosocial factors show, maternal separation animal model was used and it is early life stress. The stress had induced colonic hyper-contraction, gastric hypersensitivity, and delayed emptying. The precise molecular mechanisms are still under investigations.

scholarly journals Cryo-EM structural studies of the agonist complexed human TRPV4 ion-channel reveals novel structural rearrangements resulting in an open-conformation

2020 ◽  
Author(s):  
Mathieu Botte ◽  
Alexander K. C. Ulrich ◽  
Ricardo Adaixo ◽  
David Gnutt ◽  
Andreas Brockmann ◽  
...  
Keyword(s):  
Ion Channel ◽  
Binding Site ◽  
Molecular Mechanisms ◽  
Transient Receptor Potential ◽  
Structural Information ◽  
Critical Role ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Open Conformation ◽  
Transient Receptor

ABSTRACTThe human transient receptor potential vanilloid 4 (hTRPV4) ion channel plays a critical role in a variety of biological processes. Whilst the activation of hTRPV4 gating properties has been reported for a broad spectrum of stimuli, including synthetic 4α-phorbols, the molecular basis of the activation is poorly understood. Here we report the novel cryo-EM structure of the hTRPV4 determined in the presence of the archetypical phorbol acid agonist, 4α-PDD. Complementary mutagenesis experiments support the EM-identified binding site as well as allowing rationalization of disruptive mutants located outside of the 4α-PDD binding site. This work represents the first structural information of hTRPV4 in a ligand-induced open conformation. Together, our data reveal the underlying molecular mechanisms resulting in the opening of the central pore and ion-channel activation and provide a structural template for designing inhibitors targeting the open-state conformation of hTRPV4.

The Transient Receptor Potential Vanilloid Type 1 Ion Channel in Hypometabolic Response to Hypoxia

2018 ◽  
Author(s):  
Brian Foo
Keyword(s):  
Body Temperature ◽  
Ion Channel ◽  
Molecular Mechanisms ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Trpv1 Receptor ◽  
Transient Receptor ◽  
Knockout Animals

When challenged with low levels of available oxygen (hypoxia), larger mammals, including humans, attempt to maintain a consistent oxygen supply by increasing their rate of respiration. Smaller rodents and newborn mammals, on the other hand, respond to hypoxia by curtailing oxygen consumption. This latter process (hypoxic hypometabolism) involves actively regulated reductions in both metabolic rate and body temperature (3; 4; 9). Despite more than 50 years of investigation, the molecular mechanisms of this intriguing process are still unclear. Recently, the transient receptor potential vanilloid type 1 (TRPV1) receptor (best known for its response to capsaicin) has been implicated in the regulation of body temperature (5). Evidence includes the ability of TRPV1 receptor agonists and antagonists to lower and raise body temperature respectively (6; 7), as well as a demonstrated site of action within thehypothalamus (the area of the brain responsible for the regulation of body temperature) (1; 2). Based on the parallel but separately identified roles of hypoxia and TRPV1 in controlling body temperature, we reasoned that the TRPV1 ion channel may be implicated in hypoxia-induced alterations in body temperature. This present study investigates the potential involvement of the TRPV1 ion channel in hypoxia mediated hypothermia by comparing the hypoxic responses of wild-type mice and transgenetic knockout animals lacking a functional TRPV1 gene. We hypothesize that the TRPV1 knockout animals will show a blunted hypothermic response to hypoxic challenge. 

scholarly journals Supercooling Agent Icilin Blocks a Warmth-Sensing Ion Channel TRPV3

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Muhammad Azhar Sherkheli ◽  
Guenter Gisselmann ◽  
Hanns Hatt
Keyword(s):  
Ion Channel ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Human Keratinocytes ◽  
Transient Receptor Potential Vanilloid ◽  
Neural Cells ◽  
Hek 293 ◽  
Low Concentrations ◽  
293 Cells ◽  
Transient Receptor

Transient receptor potential vanilloid subtype 3 (TRPV3) is a thermosensitive ion channel expressed in a variety of neural cells and in keratinocytes. It is activated by warmth (33–39°C), and its responsiveness is dramatically increased at nociceptive temperatures greater than 40°C. Monoterpenoids and 2-APB are chemical activators of TRPV3 channels. We found that Icilin, a known cooling substance and putative ligand of TRPM8, reversibly inhibits TRPV3 activity at nanomolar concentrations in expression systems likeXenopus laevesoocytes, HEK-293 cells, and in cultured human keratinocytes. Our data show that icilin's antagonistic effects for the warm-sensitive TRPV3 ion channel occurs at very low concentrations. Therefore, the cooling effect evoked by icilin may at least in part be due to TRPV3 inhibition in addition to TRPM8 potentiation. Blockade of TRPV3 activity by icilin at such low concentrations might have important implications for overall cooling sensations detected by keratinocytes and free nerve endings in skin. We hypothesize that blockage of TRPV3 might be a signal for cool-sensing systems (like TRPM8) to beat up the basal activity resulting in increased cold perception when warmth sensors (like TRPV3) are shut off.

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