scholarly journals Epithelial transient receptor potential ankyrin 1 (TRPA1)-dependent adrenomedullin upregulates blood flow in rat small intestine

2013 ◽  
Vol 304 (4) ◽  
pp. G428-G436 ◽  
Author(s):  
Toru Kono ◽  
Atsushi Kaneko ◽  
Yuji Omiya ◽  
Katsuya Ohbuchi ◽  
Nagisa Ohno ◽  
...  
Keyword(s):  
Blood Flow ◽  
Small Intestine ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Allyl Isothiocyanate ◽  
Antibody Treatment ◽  
Functional Roles ◽  
Transient Receptor

The functional roles of transient receptor potential (TRP) channels in the gastrointestinal tract have garnered considerable attention in recent years. We previously reported that daikenchuto (TU-100), a traditional Japanese herbal medicine, increased intestinal blood flow (IBF) via adrenomedullin (ADM) release from intestinal epithelial (IE) cells (Kono T et al. J Crohns Colitis 4: 161–170, 2010). TU-100 contains multiple TRP activators. In the present study, therefore, we examined the involvement of TRP channels in the ADM-mediated vasodilatatory effect of TU-100. Rats were treated intraduodenally with the TRP vanilloid type 1 (TRPV1) agonist capsaicin (CAP), the TRP ankyrin 1 (TRPA1) agonist allyl-isothiocyanate (AITC), or TU-100, and jejunum IBF was evaluated using laser-Doppler blood flowmetry. All three compounds resulted in vasodilatation, and the vasodilatory effect of TU-100 was abolished by a TRPA1 antagonist but not by a TRPV1 antagonist. Vasodilatation induced by AITC and TU-100 was abrogated by anti-ADM antibody treatment. RT-PCR and flow cytometry revealed that an IEC-6 cell line originated from the small intestine and purified IE cells expressed ADM and TRPA1 but not TRPV1. AITC increased ADM release in IEC cells remarkably, while CAP had no effect. TU-100 and its ingredient 6-shogaol (6SG) increased ADM release dose-dependently, and the effects were abrogated by a TRPA1 antagonist. 6SG showed similar TRPA1-dependent vasodilatation in vivo. These results indicate that TRPA1 in IE cells may play an important role in controlling bowel microcirculation via ADM release. Epithelial TRPA1 appears to be a promising target for the development of novel strategies for the treatment of various gastrointestinal disorders.

scholarly journals Functional Interaction among KCa and TRP Channels for Cardiovascular Physiology: Modern Perspectives on Aging and Chronic Disease

2019 ◽  
Vol 20 (6) ◽  
pp. 1380 ◽  
Author(s):  
Erik Behringer ◽  
Md Hakim
Keyword(s):  
Blood Flow ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
The Body ◽  
Cardiovascular Physiology ◽  
Treatment And Prevention ◽  
Kca Channels ◽  
Age Related ◽  
Transient Receptor

Effective delivery of oxygen and essential nutrients to vital organs and tissues throughout the body requires adequate blood flow supplied through resistance vessels. The intimate relationship between intracellular calcium ([Ca2+]i) and regulation of membrane potential (Vm) is indispensable for maintaining blood flow regulation. In particular, Ca2+-activated K+ (KCa) channels were ascertained as transducers of elevated [Ca2+]i signals into hyperpolarization of Vm as a pathway for decreasing vascular resistance, thereby enhancing blood flow. Recent evidence also supports the reverse role for KCa channels, in which they facilitate Ca2+ influx into the cell interior through open non-selective cation (e.g., transient receptor potential; TRP) channels in accord with robust electrical (hyperpolarization) and concentration (~20,000-fold) transmembrane gradients for Ca2+. Such an arrangement supports a feed-forward activation of Vm hyperpolarization while potentially boosting production of nitric oxide. Furthermore, in vascular types expressing TRP channels but deficient in functional KCa channels (e.g., collecting lymphatic endothelium), there are profound alterations such as downstream depolarizing ionic fluxes and the absence of dynamic hyperpolarizing events. Altogether, this review is a refined set of evidence-based perspectives focused on the role of the endothelial KCa and TRP channels throughout multiple experimental animal models and vascular types. We discuss the diverse interactions among KCa and TRP channels to integrate Ca2+, oxidative, and electrical signaling in the context of cardiovascular physiology and pathology. Building from a foundation of cellular biophysical data throughout a wide and diverse compilation of significant discoveries, a translational narrative is provided for readers toward the treatment and prevention of chronic, age-related cardiovascular disease.

Intragastric administration of allyl isothiocyanate increases carbohydrate oxidation via TRPV1 but not TRPA1 in mice

2011 ◽  
Vol 300 (6) ◽  
pp. R1494-R1505 ◽  
Author(s):  
Noriyuki Mori ◽  
Fuminori Kawabata ◽  
Shigenobu Matsumura ◽  
Hiroshi Hosokawa ◽  
Shigeo Kobayashi ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Allyl Isothiocyanate ◽  
Carbohydrate Oxidation ◽  
Trp Channel ◽  
Ion Concentration ◽  
Intragastric Administration ◽  
Intracellular Calcium Ion ◽  
Transient Receptor

The transient receptor potential (TRP) channel family is composed of a wide variety of cation-permeable channels activated polymodally by various stimuli and is implicated in a variety of cellular functions. Recent investigations have revealed that activation of TRP channels is involved not only in nociception and thermosensation but also in thermoregulation and energy metabolism. We investigated the effect of intragastric administration of TRP channel agonists on changes in energy substrate utilization of mice. Intragastric administration of allyl isothiocyanate (AITC; a typical TRPA1 agonist) markedly increased carbohydrate oxidation but did not affect oxygen consumption. To examine whether TRP channels mediate this increase in carbohydrate oxidation, we used TRPA1 and TRPV1 knockout (KO) mice. Intragastric administration of AITC increased carbohydrate oxidation in TRPA1 KO mice but not in TRPV1 KO mice. Furthermore, AITC dose-dependently increased intracellular calcium ion concentration in cells expressing TRPV1. These findings suggest that AITC might activate TRPV1 and that AITC increased carbohydrate oxidation via TRPV1.

scholarly journals Functional Importance of Transient Receptor Potential (TRP) Channels in Neurological Disorders

2021 ◽  
Vol 9 ◽  
Author(s):  
Kihwan Lee ◽  
Youn Yi Jo ◽  
Gehoon Chung ◽  
Jung Hoon Jung ◽  
Yong Ho Kim ◽  
...  
Keyword(s):  
Neurological Disorders ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Protein Complexes ◽  
Transmembrane Protein ◽  
Second Messengers ◽  
Ion Homeostasis ◽  
Receptor Potential ◽  
Functional Roles ◽  
Transient Receptor

Transient receptor potential (TRP) channels are transmembrane protein complexes that play important roles in the physiology and pathophysiology of both the central nervous system (CNS) and the peripheral nerve system (PNS). TRP channels function as non-selective cation channels that are activated by several chemical, mechanical, and thermal stimuli as well as by pH, osmolarity, and several endogenous or exogenous ligands, second messengers, and signaling molecules. On the pathophysiological side, these channels have been shown to play essential roles in the reproductive system, kidney, pancreas, lung, bone, intestine, as well as in neuropathic pain in both the CNS and PNS. In this context, TRP channels have been implicated in several neurological disorders, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and epilepsy. Herein, we focus on the latest involvement of TRP channels, with a special emphasis on the recently identified functional roles of TRP channels in neurological disorders related to the disruption in calcium ion homeostasis.

scholarly journals Mechanotransduction of the endothelial glycocalyx mediates nitric oxide production through activation of TRP channels

2016 ◽  
Vol 311 (6) ◽  
pp. C846-C853 ◽  
Author(s):  
Matthew A. Dragovich ◽  
Daniel Chester ◽  
Bingmei M. Fu ◽  
Chenyu Wu ◽  
Yan Xu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Mechanical Stretch ◽  
Endothelial Glycocalyx ◽  
No Production ◽  
Endothelial Surface ◽  
Transient Receptor

The endothelial surface glycocalyx (ESG) is a carbohydrate-rich layer found on the vascular endothelium, serving critical functions in the mechanotransduction of blood flow-induced forces. One of the most important protective functions of the ESG is to mediate the production of nitric oxide (NO) in response to blood flow. However, the detailed mechanism underlying ESG's mechanotransduction of the production of NO has not been completely identified. Herein, using the cultured rat brain microvascular endothelial cells (bEnd.3) as a model system, we have implemented a combined atomic force and fluorescence microscopy approach to show that the ESG senses and transduces vertical mechanical stretch to produce NO. This rapid NO production is dependent on the presence of both heparan sulfate (HS) and hyaluronic acid (HA) in ESG, as the removal of HS and/or HA leads to a significant decrease in NO production. Moreover, the production of NO is dependent on the intake of Ca2+ via endothelial transient receptor potential (TRP) channels. Together, our results demonstrate the molecular mechanism of rapid production of NO in response to vertical mechanical stretch.

scholarly journals Transient Receptor Potential Channel Expression Signatures in Tumor-Derived Endothelial Cells: Functional Roles in Prostate Cancer Angiogenesis

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 956 ◽  
Author(s):  
Michela Bernardini ◽  
Alessia Brossa ◽  
Giorgia Chinigo ◽  
Guillaume P. Grolez ◽  
Giulia Trimaglio ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Angiogenic Factor ◽  
Renal Tumors ◽  
Transient Receptor

Background: Transient receptor potential (TRP) channels control multiple processes involved in cancer progression by modulating cell proliferation, survival, invasion and intravasation, as well as, endothelial cell (EC) biology and tumor angiogenesis. Nonetheless, a complete TRP expression signature in tumor vessels, including in prostate cancer (PCa), is still lacking. Methods: In the present study, we profiled by qPCR the expression of all TRP channels in human prostate tumor-derived ECs (TECs) in comparison with TECs from breast and renal tumors. We further functionally characterized the role of the ‘prostate-associated’ channels in proliferation, sprout formation and elongation, directed motility guiding, as well as in vitro and in vivo morphogenesis and angiogenesis. Results: We identified three ‘prostate-associated’ genes whose expression is upregulated in prostate TECs: TRPV2 as a positive modulator of TEC proliferation, TRPC3 as an endothelial PCa cell attraction factor and TRPA1 as a critical TEC angiogenic factor in vitro and in vivo. Conclusions: We provide here the full TRP signature of PCa vascularization among which three play a profound effect on EC biology. These results contribute to explain the aggressive phenotype previously observed in PTEC and provide new putative therapeutic targets.

scholarly journals Small-molecule activation of lysosomal TRP channels ameliorates Duchenne muscular dystrophy in mouse models

2020 ◽  
Vol 6 (6) ◽  
pp. eaaz2736 ◽  
Author(s):  
Lu Yu ◽  
Xiaoli Zhang ◽  
Yexin Yang ◽  
Dan Li ◽  
Kaiyuan Tang ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Elevated Serum ◽  
Receptor Potential ◽  
Small Molecule Activation ◽  
Activation Of Transcription ◽  
Transient Receptor

Duchenne muscular dystrophy (DMD) is a devastating disease caused by mutations in dystrophin that compromise sarcolemma integrity. Currently, there is no treatment for DMD. Mutations in transient receptor potential mucolipin 1 (ML1), a lysosomal Ca2+ channel required for lysosomal exocytosis, produce a DMD-like phenotype. Here, we show that transgenic overexpression or pharmacological activation of ML1 in vivo facilitates sarcolemma repair and alleviates the dystrophic phenotypes in both skeletal and cardiac muscles of mdx mice (a mouse model of DMD). Hallmark dystrophic features of DMD, including myofiber necrosis, central nucleation, fibrosis, elevated serum creatine kinase levels, reduced muscle force, impaired motor ability, and dilated cardiomyopathies, were all ameliorated by increasing ML1 activity. ML1-dependent activation of transcription factor EB (TFEB) corrects lysosomal insufficiency to diminish muscle damage. Hence, targeting lysosomal Ca2+ channels may represent a promising approach to treat DMD and related muscle diseases.

scholarly journals Expression of Transient Receptor Potential Ankyrin 1 and Transient Receptor Potential Vanilloid 1 in the Gut of the Peri-Weaning Pig Is Strongly Dependent on Age and Intestinal Site

Animals ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 2417
Author(s):  
Elout Van Liefferinge ◽  
Noémie Van Noten ◽  
Jeroen Degroote ◽  
Gunther Vrolix ◽  
Mario Van Poucke ◽  
...  
Keyword(s):  
Small Intestine ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
The Body ◽  
Enteroendocrine Cells ◽  
Sensory Transduction ◽  
Transient Receptor Potential Vanilloid ◽  
Distal Small Intestine ◽  
Transient Receptor

Transient receptor potential (TRP) channels contribute to sensory transduction in the body, agonized by a variety of stimuli, such as phytochemicals, and they are predominantly distributed in afferent neurons. Evidence indicates their expression in non-neuronal cells, demonstrating their ability to modulate gastrointestinal function. Targeting TRP channels could potentially be used to regulate gastrointestinal secretion and motility, yet their expression in the pig is unknown. This study investigated TRPA1 and TRPV1 expression in different gut locations of piglets of varying age. Colocalization with enteroendocrine cells was established by immunohistochemistry. Both channels were expressed in the gut mucosa. TRPV1 mRNA abundance increased gradually in the stomach and small intestine with age, most notably in the distal small intestine. In contrast, TRPA1 exhibited sustained expression across ages and locations, with the exception of higher expression in the pylorus at weaning. Immunohistochemistry confirmed the endocrine nature of both channels, showing the highest frequency of colocalization in enteroendocrine cells for TRPA1. Specific co-localization on GLP-1 immunoreactive cells indicated their possible role in GLP-1 release and the concomitant intestinal feedback mechanism. Our results indicate that TRPA1 and TRPV1 could play a role in gut enteroendocrine activity. Moreover, age and location in the gut significantly affected gene expression.

scholarly journals Internal Ca2+ release in yeast is triggered by hypertonic shock and mediated by a TRP channel homologue

2002 ◽  
Vol 156 (1) ◽  
pp. 29-34 ◽  
Author(s):  
Valérie Denis ◽  
Martha S. Cyert
Keyword(s):  
Mammalian Cells ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Second Messengers ◽  
Receptor Potential ◽  
Ip3 Receptors ◽  
Intracellular Compartments ◽  
No Signaling ◽  
Transient Receptor

Calcium ions, present inside all eukaryotic cells, are important second messengers in the transduction of biological signals. In mammalian cells, the release of Ca2+ from intracellular compartments is required for signaling and involves the regulated opening of ryanodine and inositol-1,4,5-trisphosphate (IP3) receptors. However, in budding yeast, no signaling pathway has been shown to involve Ca2+ release from internal stores, and no homologues of ryanodine or IP3 receptors exist in the genome. Here we show that hyperosmotic shock provokes a transient increase in cytosolic Ca2+ in vivo. Vacuolar Ca2+, which is the major intracellular Ca2+ store in yeast, is required for this response, whereas extracellular Ca2+ is not. We aimed to identify the channel responsible for this regulated vacuolar Ca2+ release. Here we report that Yvc1p, a vacuolar membrane protein with homology to transient receptor potential (TRP) channels, mediates the hyperosmolarity induced Ca2+ release. After this release, low cytosolic Ca2+ is restored and vacuolar Ca2+ is replenished through the activity of Vcx1p, a Ca2+/H+ exchanger. These studies reveal a novel mechanism of internal Ca2+ release and establish a new function for TRP channels.

scholarly journals Remedia Sternutatoria over the Centuries: TRP Mediation

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1627
Author(s):  
Lujain Aloum ◽  
Eman Alefishat ◽  
Janah Shaya ◽  
Georg A. Petroianu
Keyword(s):  
Transient Receptor Potential ◽  
Trp Channels ◽  
Sensory Nerve ◽  
Receptor Potential ◽  
Allyl Isothiocyanate ◽  
The Body ◽  
Trp Channel ◽  
Nerve Terminals ◽  
Present Contribution ◽  
Transient Receptor

Sneezing (sternutatio) is a poorly understood polysynaptic physiologic reflex phenomenon. Sneezing has exerted a strange fascination on humans throughout history, and induced sneezing was widely used by physicians for therapeutic purposes, on the assumption that sneezing eliminates noxious factors from the body, mainly from the head. The present contribution examines the various mixtures used for inducing sneezes (remedia sternutatoria) over the centuries. The majority of the constituents of the sneeze-inducing remedies are modulators of transient receptor potential (TRP) channels. The TRP channel superfamily consists of large heterogeneous groups of channels that play numerous physiological roles such as thermosensation, chemosensation, osmosensation and mechanosensation. Sneezing is associated with the activation of the wasabi receptor, (TRPA1), typical ligand is allyl isothiocyanate and the hot chili pepper receptor, (TRPV1), typical agonist is capsaicin, in the vagal sensory nerve terminals, activated by noxious stimulants.

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