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 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 The Xenopus tropicalis orthologue of TRPV3 is heat sensitive

2015 ◽  
Vol 146 (5) ◽  
pp. 411-421 ◽  
Author(s):  
Beiying Liu ◽  
Feng Qin
Keyword(s):  
Mammalian Cells ◽  
Xenopus Oocytes ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Expression System ◽  
Receptor Potential ◽  
Functional Expression ◽  
Cold Sensitivity ◽  
Mammalian Cell Lines ◽  
Transient Receptor

Thermosensitive members of the transient receptor potential (TRP) family of ion channels (thermal TRP channels) play a crucial role in mammalian temperature sensing. Orthologues of these channels are present in lower vertebrates and, remarkably, some thermal TRP orthologues from different species appear to mediate opposing responses to temperature. For example, whereas the mammalian TRPV3 channel is activated by heat, frog TRPV3 is reportedly activated by cold. Intrigued by the potential implications of these opposing responses to temperature for the mechanism of temperature-dependent gating, we cloned Xenopus laevis TRPV3 and functionally expressed it in both mammalian cell lines and Xenopus oocytes. We found that, when expressed in mammalian cells, the recombinant channel lacks the reported cold sensitivity; rather, it is activated by temperatures >50°C. Furthermore, when expressed in mammalian cells, the frog orthologue shows other features characteristic of mammalian TRPV3, including activation by the agonist 2-aminoethoxydiphenyl borate and an increased response with repeated stimulation. We detected both heat- and cold-activated currents in Xenopus oocytes expressing the recombinant frog TRPV3 channel. However, cold-activated currents were also apparent in control oocytes lacking recombinant TRPV3. Our data indicate that frog TRPV3 resembles its mammalian orthologues in terms of its thermosensitivity and is intrinsically activated by heat. Thus, all known vanilloid receptors are activated by heat. Our data also show that Xenopus oocytes contain endogenous receptors that are activated by cold, and suggest that cold sensitivity of TRP channels established using Xenopus oocytes as a functional expression system may need to be revisited.

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 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 Homer 1 Mediates Store- and Inositol 1,4,5-Trisphosphate Receptor-dependent Translocation and Retrieval of TRPC3 to the Plasma Membrane

2006 ◽  
Vol 281 (43) ◽  
pp. 32540-32549 ◽  
Author(s):  
Joo Young Kim ◽  
Weizong Zeng ◽  
Kirill Kiselyov ◽  
Joseph P. Yuan ◽  
Marlin H. Dehoff ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Mammalian Cells ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Trp Channel ◽  
Resting Cells ◽  
Agonist Stimulation ◽  
Intracellular Vesicles ◽  
Transient Receptor

Store-operated Ca2+ channels (SOCs) mediate receptor-stimulated Ca2+ influx. Accumulating evidence indicates that members of the transient receptor potential (TRP) channel family are components of SOCs in mammalian cells. Agonist stimulation activates SOCs and TRP channels directly and by inducing translocation of channels in intracellular vesicles to the plasma membrane (PM). The mechanism of TRP channel translocation in response to store depletion and agonist stimulation is not known. Here we use TRPC3 as a model to show that IP3 and the scaffold Homer 1 (H1) regulate the rate of translocation and retrieval of TRPC3 from the PM. In resting cells, TRPC3 exists in TRPC3-H1b/c-IP3Rs complexes that are located in part at the PM and in part in intracellular vesicles. Binding of IP3 to the IP3Rs dissociates the interaction between IP3Rs and H1 but not between H1 and TRPC3 to form IP3Rs-TRPC3-H1b/c. TIRFM and biotinylation assays show robust receptor- and store-dependent translocation of the TRPC3 to the PM and their retrieval upon termination of cell stimulation. The translocation requires depletion of stored Ca2+ and is prevented by inhibition of the IP3Rs. In HEK293, dissociating the H1b/c-IP3R complex with H1a results in TRPC3 translocation to the PM, where it is spontaneously active. The TRPC3-H1b/c-IP3Rs complex is reconstituted by infusing H1c into these cells. Reconstitution is inhibited by IP3. Deletion of H1 in mice markedly reduces the rates of translocation and retrieval of TRPC3. Conversely, infusion of H1c into H1-/- cells eliminates spontaneous channel activity and increases the rate of channel activation by agonist stimulation. The effects of H1c are inhibited by IP3. These findings together with our earlier studies demonstrating gating of TRPC3 by IP3Rs were used to develop a model in which assembly of the TRPC3-H1b/c-IP3Rs complexes by H1b/c mediates both the translocation of TRPC3-containing vesicles to the PM and gating of TRPC3 by IP3Rs.

scholarly journals A capsaicinoid-based soft drug, AG1529, for attenuating TRPV1-mediated histaminergic and inflammatory sensory neuron excitability

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Magdalena Nikolaeva-Koleva ◽  
Laura Butron ◽  
Sara González-Rodríguez ◽  
Isabel Devesa ◽  
Pierluigi Valente ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Primary Cultures ◽  
Receptor Potential ◽  
Neuronal Firing ◽  
In Vivo Model ◽  
Drg Neurons ◽  
Trpv1 Channels ◽  
Soft Drug ◽  
Transient Receptor

AbstractTRPV1, a member of the transient receptor potential (TRP) family, is a nonselective calcium permeable ion channel gated by physical and chemical stimuli. In the skin, TRPV1 plays an important role in neurogenic inflammation, pain and pruritus associated to many dermatological diseases. Consequently, TRPV1 modulators could represent pharmacological tools to respond to important patient needs that still represent an unmet medical demand. Previously, we reported the design of capsaicinoid-based molecules that undergo dermal deactivation (soft drugs), thus preventing their long-term dermal accumulation. Here, we investigated the pharmacological properties of the lead antagonist, 2-((4-hydroxy-2-iodo-5-methoxybenzyl) amino)-2-oxoethyl dodecanoate (AG1529), on heterologously expressed human TRPV1 (hTRPV1), on nociceptor excitability and on an in vivo model of acute pruritus. We report that AG1529 competitively blocked capsaicin-evoked activation of hTRPV1 with micromolar potency, moderately affected pH-induced gating, and did not alter voltage- and heat-mediated responses. AG1529 displays modest receptor selectivity as it mildly blocked recombinant hTRPA1 and hTRPM8 channels. In primary cultures of rat dorsal root ganglion (DRG) neurons, AG1529 potently reduced capsaicin-evoked neuronal firing. AG1529 exhibited lower potency on pH-evoked TRPV1 firing, and TRPA1-elicited nociceptor excitability. Furthermore, AG1529 abolished histaminergic and inflammation mediated TRPV1 sensitization in primary cultures of DRG neurons. Noteworthy, dermal wiping of AG1529, either in an acetone-based formulation or in an anhydrous ointment, dose-dependently attenuated acute histaminergic itch in a rodent model. This cutaneous anti-pruritic effect was devoid of the normal nocifensive action evoked by the burning sensation of capsaicin. Taken together, these preclinical results unveil the mode of action of AG1529 on TRPV1 channels and substantiate the tenet that this capsaicinoid-based soft drug is a promising candidate for drug development as a topical anti-pruritic and anti-inflammatory medication.

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