scholarly journals Anatomical and functional characterization of a duodeno-pancreatic neural reflex that can induce acute pancreatitis

2013 ◽  
Vol 304 (5) ◽  
pp. G490-G500 ◽  
Author(s):  
Cuiping Li ◽  
Yaohui Zhu ◽  
Mohan Shenoy ◽  
Reetesh Pai ◽  
Liansheng Liu ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Cross Talk ◽  
Mechanical Stimulation ◽  
Transient Receptor Potential ◽  
Functional Characterization ◽  
Receptor Potential ◽  
Splanchnic Nerve ◽  
Mustard Oil ◽  
Myeloperoxidase Activity ◽  
Stimulation Of

Neural cross talk between visceral organs may play a role in mediating inflammation and pain remote from the site of the insult. We hypothesized such a cross talk exists between the duodenum and pancreas, and further it induces pancreatitis in response to intraduodenal toxins. A dichotomous spinal innervation serving both the duodenum and pancreas was examined, and splanchnic nerve responses to mechanical stimulation of these organs were detected. This pathway was then excited on the duodenal side by exposure to ethanol followed by luminal mustard oil to activate transient receptor potential subfamily A, member 1 (TRPA1). Ninety minutes later, pancreatic inflammation was examined. Ablation of duodenal afferents by resiniferatoxin (RTX) or blocking TRPA1 by Chembridge (CHEM)-5861528 was used to further investigate the duodeno-pancreatic neural reflex via TRPA1. ∼40% of dorsal root ganglia (DRG) from the spinal cord originated from both duodenum and pancreas via dichotomous peripheral branches; ∼50% splanchnic nerve single units responded to mechanical stimulation of both organs. Ethanol sensitized TRPA1 currents in cultured DRG neurons. Pancreatic edema and myeloperoxidase activity significantly increased after intraduodenal ethanol followed by mustard oil (but not capsaicin) but significantly decreased after ablation of duodenal afferents by using RTX or blocking TRPA1 by CHEM-5861528. We found the existence of a neural cross talk between the duodenum and pancreas that can promote acute pancreatitis in response to intraduodenal chemicals. It also proves a previously unexamined mechanism by which alcohol can induce pancreatitis, which is novel both in terms of the site (duodenum), process (neurogenic), and receptor (TRPA1).

scholarly journals Calcium signaling through a Transient Receptor Channel is important for Toxoplasma gondii growth

2020 ◽  
Author(s):  
Karla M. Márquez-Nogueras ◽  
Nathan M. Chasen ◽  
Myriam A. Hortua Triana ◽  
Ivana Y. Kuo ◽  
Silvia N.J. Moreno
Keyword(s):  
Toxoplasma Gondii ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Functional Characterization ◽  
Receptor Potential ◽  
Nuclear Membranes ◽  
Intracellular Ca ◽  
Transient Receptor ◽  
Stimulation Of ◽  
Receptor Channel

ABSTRACTTransient Receptor Potential (TRP) channels participate in ion calcium (Ca2+) influx and intracellular Ca2+ release. TRP channels have not been studied in Toxoplasma gondii or any other Apicomplexan parasite. We characterized a protein predicted to possess a TRP domain (TgTRPPL-2) and determined its role in Ca2+ signaling in T. gondii, the causative agent of toxoplasmosis. TgTRPPL-2 localized to the plasma membrane and the endoplasmic reticulum of T. gondii. The ΔTgTRPPL-2 mutant was defective in growth and Ca2+ influx. Heterologous expression of TgTRPPL-2 in HEK-3KO cells allowed its functional characterization. Patching of ER-nuclear membranes demonstrated that TgTRPPL-2 is a non-selective cation channel that conducts Ca2+. Pharmacological blockers of TgTRPPL-2 inhibited Ca2+ influx and parasite growth. This is the first report of an Apicomplexan channel that conducts Ca2+ and initiates the Ca2+ signaling cascade that culminates in the stimulation of motility, invasion and egress. TgTRPPL-2 is a potential target for combating toxoplasmosis.

scholarly journals Calcium signaling through a Transient Receptor Channel is important for Toxoplasma gondii growth

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Karla Marie Marquez-Nogueras ◽  
Myriam Andrea Hortua Triana ◽  
Nathan M Chasen ◽  
Ivana Y Kuo ◽  
Silvia NJ Moreno
Keyword(s):  
Toxoplasma Gondii ◽  
Calcium Ion ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Functional Characterization ◽  
Receptor Potential ◽  
Intracellular Ca ◽  
Transient Receptor ◽  
Stimulation Of ◽  
Receptor Channel

Transient Receptor Potential (TRP) channels participate in calcium ion (Ca2+) influx and intracellular Ca2+ release. TRP channels have not been studied in Toxoplasma gondii or any other apicomplexan parasite. In this work we characterize TgGT1_310560, a protein predicted to possess a TRP domain (TgTRPPL-2) and determined its role in Ca2+ signaling in T. gondii, the causative agent of toxoplasmosis. TgTRPPL-2 localizes to the plasma membrane and the endoplasmic reticulum (ER) of T. gondii. The ΔTgTRPPL-2 mutant was defective in growth and cytosolic Ca2+ influx from both extracellular and intracellular sources. Heterologous expression of TgTRPPL-2 in HEK-3KO cells allowed its functional characterization. Patching of ER-nuclear membranes demonstrates that TgTRPPL-2 is a non-selective cation channel that conducts Ca2+. Pharmacological blockers of TgTRPPL-2 inhibit Ca2+ influx and parasite growth. This is the first report of an apicomplexan ion channel that conducts Ca2+ and may initiate a Ca2+ signaling cascade that leads to the stimulation of motility, invasion and egress. TgTRPPL-2 is a potential target for combating Toxoplasmosis.

scholarly journals Polyamines regulate intestinal epithelial restitution through TRPC1-mediated Ca2+ signaling by differentially modulating STIM1 and STIM2

2012 ◽  
Vol 303 (3) ◽  
pp. C308-C317 ◽  
Author(s):  
Jaladanki N. Rao ◽  
Navneeta Rathor ◽  
Ran Zhuang ◽  
Tongtong Zou ◽  
Lan Liu ◽  
...  
Keyword(s):  
Cell Migration ◽  
Intestinal Epithelial Cell ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Intestinal Epithelial ◽  
Canonical Transient Receptor Potential ◽  
Pathological Conditions ◽  
Epithelial Restitution ◽  
Transient Receptor ◽  
Stimulation Of

Early epithelial restitution occurs as a consequence of intestinal epithelial cell (IEC) migration after wounding, and its defective regulation is implicated in various critical pathological conditions. Polyamines stimulate intestinal epithelial restitution, but their exact mechanism remains unclear. Canonical transient receptor potential-1 (TRPC1)-mediated Ca2+ signaling is crucial for stimulation of IEC migration after wounding, and induced translocation of stromal interaction molecule 1 (STIM1) to the plasma membrane activates TRPC1-mediated Ca2+ influx and thus enhanced restitution. Here, we show that polyamines regulate intestinal epithelial restitution through TRPC1-mediated Ca2+ signaling by altering the ratio of STIM1 to STIM2. Increasing cellular polyamines by ectopic overexpression of the ornithine decarboxylase (ODC) gene stimulated STIM1 but inhibited STIM2 expression, whereas depletion of cellular polyamines by inhibiting ODC activity decreased STIM1 but increased STIM2 levels. Induced STIM1/TRPC1 association by increasing polyamines enhanced Ca2+ influx and stimulated epithelial restitution, while decreased formation of the STIM1/TRPC1 complex by polyamine depletion decreased Ca2+ influx and repressed cell migration. Induced STIM1/STIM2 heteromers by polyamine depletion or STIM2 overexpression suppressed STIM1 membrane translocation and inhibited Ca2+ influx and epithelial restitution. These results indicate that polyamines differentially modulate cellular STIM1 and STIM2 levels in IECs, in turn controlling TRPC1-mediated Ca2+ signaling and influencing cell migration after wounding.

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.

Abstract P219: Vascular Cross-talk Between Redox and Calcium Signaling in Hypertension Involves Transient Receptor Potential Melastatin 2 Channel Activation

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Rhéure Alves-Lopes ◽  
Augusto C Montezano ◽  
Karla B Neves ◽  
Aikaterini Anagnostopoulou ◽  
Silvia Lacchini ◽  
...  
Keyword(s):  
Cross Talk ◽  
Transient Receptor Potential ◽  
Vascular Dysfunction ◽  
Receptor Potential ◽  
Mesenteric Arteries ◽  
Ang Ii ◽  
Channel Activation ◽  
Hypertensive Patients ◽  
Transient Receptor Potential Melastatin ◽  
Transient Receptor

The transient receptor potential melastatin 2 cation channel (TRPM2) is redox-sensitive and promotes Ca 2+ influx after H 2 O 2 activation through oxidative modification and PARP-ADPR-dependent mechanisms. TRPM2 also regulates Na + influx, and by increasing [Na + ]i interferes with the Na + -Ca 2+ exchanger (NCX) inducing reverse mode action, promoting Ca 2+ influx. These processes may be driven by Nox4-derived H 2 O 2. We tested the hypothesis that vascular dysfunction in hypertension involves oxidative stress-induced TRPM2 activation through H 2 O 2 production, which in turn promotes Ca 2+ influx. Mesenteric arteries isolated from wildtype (WT), LinA3 (mice expressing human renin with Ang II-dependent hypertension), Nox4 -/- and LinA3/Nox4 -/- mice and vascular smooth muscle cells (VSMCs) from hypertensive and normotensive patients were used. Arteries from hypertensive LinA3 mice, exhibit increased U46619-induced vasoconstriction versus WT mice (Emax - LinA3 vs WT: 9.37 ± 0.51 vs 6.79 ± 0.29), an effect attenuated by olaparib (PARP-ADPR inhibitor) and 2-APB (TRPM2 blocker) and also increased mRNA expression (Fold change - related to control) of NOX4 (3.05 ± 0.30), TRPM2 (1.38 ± 0.24), NCX (1.973 ± 0.34) and salt inducible kinase 1 (1.833 ± 0.12) and sodium-potassium pump (1.43 ± 0.16), which are activated when intracellular levels of Na + rise beyond a critical point. These events seem to be regulated by NOX4, since they were not observed in mesenteric arteries from LinA3/Nox4 -/- mice. Ang II-induced Ca 2+ influx is potentiated in VSMCs from hypertensive patients (AUC-Ex490/Em535: normotensive: 15400±917.5 vs hypertensive - 22460±2388), a response followed by increased generation of O 2 - and H 2 O 2 in cells from hypertensive patients. These ROS effects were attenuated by catalase, and 2-APB, 8-br and olaparib (TRPM2 inhibitors) and benzamil, KB-R7943 and YM244769 (NCX inhibitors). Our data indicate that TRPM2 ion channel activation contributes to redox-sensitive vascular dysfunction in hypertension. These findings suggest that dysregulation of TRPM2-NOX4-derived ROS and NCX may contribute to redox- and Ca 2+ signalling important in vascular function in hypertension. TRPM2 may be a point of cross-talk between ROS and Ca 2+ signalling.

Importance of melastatin-like transient receptor potential 7 and magnesium in the stimulation of osteoblast proliferation and migration by platelet-derived growth factor

2009 ◽  
Vol 297 (2) ◽  
pp. C360-C368 ◽  
Author(s):  
Elie Abed ◽  
Robert Moreau
Keyword(s):  
Growth Factor ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Platelet Derived Growth Factor ◽  
Human Osteoblast ◽  
Osteoblast Proliferation ◽  
Transient Receptor ◽  
And Migration ◽  
Stimulation Of ◽  
Proliferation And Migration

Bone is a dynamic tissue that is continuously being remodeled throughout life. Specialized cells called osteoclasts transiently break down old bone (resorption process) at multiple sites as other cells known as osteoblasts are replacing it with new tissue (bone formation). Usually, both resorption and formation processes are in balance and thereby maintain skeletal strength and integrity. This equilibrium is assured by the coordination of proliferation, migration, differentiation, and secretory functions of the osteoblasts, which are essential for adequate formation and resorption processes. Disturbances of this equilibrium may lead to decreased bone mass (osteoporosis), increased bone fragility, and susceptibility to fractures. Epidemiological studies have linked insufficient dietary magnesium (Mg2+) intake in humans with low bone mass and osteoporosis. Here, we investigated the roles of Mg2+ and melastatin-like transient receptor potential 7 (TRPM7), known as Mg2+ channels, in human osteoblast cell proliferation and migration induced by platelet-derived growth factor (PDGF), which has been involved in the bone remodeling process. PDGF promoted an influx of Mg2+, enhanced cell migration, and stimulated the gene expression of TRPM7 channels in human osteoblast MG-63 cells. The stimulation of osteoblast proliferation and migration by PDGF was significantly reduced under culture conditions of low extracellular Mg2+ concentrations. Silencing TRPM7 expression in osteoblasts by specific small interfering RNA prevented the induction by PDGF of Mg2+ influx, proliferation, and migration. Our results indicate that extracellular Mg2+ and TRPM7 are important for PDGF-induced proliferation and migration of human osteoblasts. Thus Mg2+ deficiency, a common condition among the general population, may be associated with altered osteoblast functions leading to inadequate bone formation and the development of osteoporosis.

Sign in / Sign up

Export Citation Format

Share Document