scholarly journals Role of Serosal TRPV4-Constituted SOCE Mechanism in Secretagogues-Stimulated Intestinal Epithelial Anion Secretion

2021 ◽  
Vol 12 ◽  
Author(s):  
Yinghui Cui ◽  
Fenglan Chu ◽  
Kai Yin ◽  
Xiongying Chen ◽  
Hanxing Wan ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Transient Receptor Potential ◽  
Short Circuit ◽  
Ryanodine Receptors ◽  
Transient Receptor Potential Vanilloid ◽  
Intestinal Epithelial ◽  
Free Solution ◽  
Anion Secretion ◽  
Ussing Chambers

As little is known about the role of calcium (Ca2+) signaling mediating the small intestinal epithelial anion secretion, we aimed to study its regulatory role in secretagogue-stimulated duodenal anion secretion and the underlying molecular mechanisms. Therefore, intestinal anion secretion from native mouse duodenal epithelia was examined with Ussing chambers to monitor PGE2-, 5-HT-, and CCh-induced short-circuit currents (Isc). PGE2 (10 μM) and 5-HT (10 μM) induced mouse duodenal Isc, markedly attenuated by serosal Ca2+-free solution and selective blockers of store-operated Ca2+ channels on the serosal side of the duodenum. Furthermore, PGE2- and 5-HT-induced duodenal Isc was also inhibited by ER Ca2+ chelator TPEN. However, dantrolene, a selective blocker of ryanodine receptors, inhibited PGE2-induced duodenal Isc, while LiCl, an inhibitor of IP3 production, inhibited 5-HT-induced Isc. Moreover, duodenal Isc response to the serosal applications of both PGE2 and 5-HT was significantly attenuated in transient receptor potential vanilloid 4 (TRPV4) knockout mice. Finally, mucosal application of carbachol (100 μM) also induced duodenal Isc via selective activation of muscarinic receptors, which was significantly inhibited in serosal Ca2+-free solution but neither in mucosal Ca2+-free solution nor by nifedipine. Therefore, the serosal TRPV4-constituted SOCE mechanism is likely universal for the most common and important secretagogues-induced and Ca2+-dependent intestinal anion secretion. These findings will enhance our knowledge about gastrointestinal (G.I.) epithelial physiology and the associated G.I. diseases, such as diarrhea and constipation.

Alterations in airway ion transport in NKCC1-deficient mice

2001 ◽  
Vol 281 (2) ◽  
pp. C615-C623 ◽  
Author(s):  
B. R. Grubb ◽  
A. J. Pace ◽  
E. Lee ◽  
B. H. Koller ◽  
R. C. Boucher
Keyword(s):  
Short Circuit ◽  
Short Circuit Current ◽  
Airway Disease ◽  
Treatment Protocols ◽  
Anion Secretion ◽  
Ussing Chambers ◽  
Adult Mice ◽  
Ion Substitution ◽  
Deficient Mice

Airways of Na+-K+-2Cl−(NKCC1)-deficient mice (−/−) were studied in Ussing chambers to determine the role of the basolateral NKCC1 in transepithelial anion secretion. The basal short-circuit current ( I sc) of tracheae and bronchi from adult mice did not differ between NKCC1−/− and normal mice, whereas NKCC1−/− tracheae from neonatal mice exhibited a significantly reduced basal I sc. In normal mouse tracheae, sensitivity to the NKCC1 inhibitor bumetanide correlated inversely with the age of the mouse. In contrast, tracheae from NKCC1−/− mice at all ages were insensitive to bumetanide. The anion secretory response to forskolin did not differ between normal and NKCC1−/− tissues. However, when larger anion secretory responses were induced with UTP, airways from the NKCC1−/− mice exhibited an attenuated response. Ion substitution and drug treatment protocols suggested that HCO[Formula: see text]secretion compensated for reduced Cl− secretion in NKCC1−/− airway epithelia. The absence of spontaneous airway disease or pathology in airways from the NKCC1−/− mice suggests that the NKCC1 mutant mice are able to compensate adequately for absence of the NKCC1 protein.

scholarly journals Integration of thermal and osmotic regulation of water homeostasis: the role of TRPV channels

2013 ◽  
Vol 305 (7) ◽  
pp. R669-R678 ◽  
Author(s):  
Celia D. Sladek ◽  
Alan Kim Johnson
Keyword(s):  
Water Loss ◽  
Molecular Mechanisms ◽  
Transient Receptor Potential ◽  
Extracellular Fluid ◽  
Transient Receptor Potential Vanilloid ◽  
Osmotic Regulation ◽  
Evaporative Water ◽  
Water Homeostasis ◽  
Vasopressin Secretion

Maintenance of body water homeostasis is critical for preventing hyperthermia, because evaporative cooling is the most efficient means of dissipating excess body heat. Water homeostasis is achieved by regulation of water intake and water loss by the kidneys. The former is achieved by sensations of thirst that motivate water acquisition, whereas the latter is regulated by the antidiuretic action of vasopressin. Vasopressin secretion and thirst are stimulated by increases in the osmolality of the extracellular fluid as well as decreases in blood pressure and/or blood volume, signals that are precipitated by water depletion associated with the excess evaporative water loss required to prevent hyperthermia. In addition, they are stimulated by increases in body temperature. The sites and molecular mechanisms involved in integrating thermal and osmotic regulation of thirst and vasopressin secretion are reviewed here with a focus on the role of the thermal and mechanosensitive transient receptor potential-vanilloid (TRPV) family of ion channels.

scholarly journals A Unique Role Of TRPV1 Ion Channels In The Suppression Of Gastric Cancer Development

2020 ◽  
Author(s):  
Nannan Gao ◽  
Feng Yang ◽  
Siyuan Chen ◽  
Hanxing Wan ◽  
Xiaoyan Zhao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Molecular Mechanisms ◽  
Transient Receptor Potential ◽  
Peritoneal Dissemination ◽  
Migration And Invasion ◽  
Transient Receptor Potential Vanilloid ◽  
Aberrant Expression ◽  
Trpv1 Channels

Abstract Background: Although the aberrant expression and function of most Ca2+-permeable channels are known to promote gastrointestinal tumors, the association of transient receptor potential vanilloid receptor 1(TRPV1) channels and gastric cancer (GC) has not been explored so far. We sought to determine their role in the development of GC and to elucidate the underlying molecular mechanisms. Methods: The expression of TRPV1 in GC cells and tissues was detected by qPCR, immunohistochemistry, western blot analysis and immunofluorescence. CCK8 and flow cytometry were used to detect the proliferation and cell cycle, while transwell assay was used to detect migration and invasion. The role of TRPV1 in GC development in vivo was tested using tumor xenograft and peritoneal dissemination assays in nude mice. Results: The decreased expression of TRPV1 protein in primary human GC tissues was closely correlated with poor prognosis of GC patients. TRPV1 protein was predominately expressed on the plasma membrane of several GC cell lines. TRPV1 overexpression attenuated proliferation, migration and invasion of GC cells in vitro, but TRPV1 knockdown increased them. Moreover, TRPV1 significantly reduced gastric tumor sizes, numbers and peritoneal dissemination in vivo. Mechanistically, TRPV1 overexpression increased [Ca2+]i, activated CaMKKβ and AMPK phosphorylation, and decreased expression of cyclin D1 and MMP2, but TRPV1 knockdown caused the opposite effects.Conclusions: TRPV1 uniquely suppresses GC through a novel Ca2+/CaMKKβ/AMPK pathway and its downregulation is correlated with poor survival in human GC. TRPV1 upregulation and its downstream signaling may be a promising strategy for GC prevention and therapy.

scholarly journals Interactions between Chemesthesis and Taste: Role of TRPA1 and TRPV1

2021 ◽  
Vol 22 (7) ◽  
pp. 3360
Author(s):  
Mee-Ra Rhyu ◽  
Yiseul Kim ◽  
Vijay Lyall
Keyword(s):  
Transient Receptor Potential ◽  
Taste Receptor ◽  
Sensory Nerve ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Trpv1 Channels ◽  
Trigeminal Neurons ◽  
Calcitonin Gene ◽  
Transient Receptor

In addition to the sense of taste and olfaction, chemesthesis, the sensation of irritation, pungency, cooling, warmth, or burning elicited by spices and herbs, plays a central role in food consumption. Many plant-derived molecules demonstrate their chemesthetic properties via the opening of transient receptor potential ankyrin 1 (TRPA1) and transient receptor potential vanilloid 1 (TRPV1) channels. TRPA1 and TRPV1 are structurally related thermosensitive cation channels and are often co-expressed in sensory nerve endings. TRPA1 and TRPV1 can also indirectly influence some, but not all, primary taste qualities via the release of substance P and calcitonin gene-related peptide (CGRP) from trigeminal neurons and their subsequent effects on CGRP receptor expressed in Type III taste receptor cells. Here, we will review the effect of some chemesthetic agonists of TRPA1 and TRPV1 and their influence on bitter, sour, and salt taste qualities.

scholarly journals Transient Receptor Potential Vanilloid in the Brain Gliovascular Unit: Prospective Targets in Therapy

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 334
Author(s):  
Huilong Luo ◽  
Xavier Declèves ◽  
Salvatore Cisternino
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Brain Diseases ◽  
Transient Receptor Potential Vanilloid ◽  
Main Role ◽  
Trpv Channels ◽  
Gliovascular Unit ◽  
Transient Receptor ◽  
The Brain

The gliovascular unit (GVU) is composed of the brain microvascular endothelial cells forming blood–brain barrier and the neighboring surrounding “mural” cells (e.g., pericytes) and astrocytes. Modulation of the GVU/BBB features could be observed in a variety of vascular, immunologic, neuro-psychiatric diseases, and cancers, which can disrupt the brain homeostasis. Ca2+ dynamics have been regarded as a major factor in determining BBB/GVU properties, and previous studies have demonstrated the role of transient receptor potential vanilloid (TRPV) channels in modulating Ca2+ and BBB/GVU properties. The physiological role of thermosensitive TRPV channels in the BBB/GVU, as well as their possible therapeutic potential as targets in treating brain diseases via preserving the BBB are reviewed. TRPV2 and TRPV4 are the most abundant isoforms in the human BBB, and TRPV2 was evidenced to play a main role in regulating human BBB integrity. Interspecies differences in TRPV2 and TRPV4 BBB expression complicate further preclinical validation. More studies are still needed to better establish the physiopathological TRPV roles such as in astrocytes, vascular smooth muscle cells, and pericytes. The effect of the chronic TRPV modulation should also deserve further studies to evaluate their benefit and innocuity in vivo.

Intra-arterial instillation of a nociceptive agent modulate cardiorespiratory parameters involving 5-HT3 and TRPV1 receptors in anesthetized rats

2021 ◽  
Vol 21 ◽  
Author(s):  
Sanjeev K. Singh ◽  
M. S. Muthu ◽  
Ravindran Revand ◽  
M. B. Mandal
Keyword(s):  
Transient Receptor Potential ◽  
Sensory Nerve ◽  
Receptor Potential ◽  
Neural Mechanisms ◽  
Transient Receptor Potential Vanilloid ◽  
Anesthetized Rats ◽  
Trpv1 Receptors ◽  
Perivascular Nerves ◽  
Transient Receptor

Background: Since long back, it has been a matter of discussion regarding the role of peripheral blood vessels in regulation of cardiorespiratory (CVR) system. Objective: The role of 5-HT3 and TRPV1 receptors present on perivascular nerves in elicitation of CVR reflexes was examined after intra-arterial instillation of bradykinin in urethane anesthetized rats. Materials and Methods: Femoral artery was cannulated retrogradely and was utilized for the instillation of saline/agonist/antagonist and recording of blood pressure (BP), using a double ported 24G cannula. BP, respiration and ECG were recorded for 30 min after bradykinin (1 µM) in the absence or presence of antagonists. Results: Instillation of bradykinin produced immediate hypotensive (40%), bradycardiac (17%), tachypnoeic (45%) and hyperventilatory (96%) responses of shorter latencies (5-8 s) favoring the neural mechanisms in producing the responses. In lignocaine (2%) pretreated animals, bradykinin-induced hypotensive (10%), bradycardiac (1.7%), tachypnoeic (13%) and hyperventilatory (13%) responses attenuated significantly. Pretreatment with ondansetron (100 µg/kg), 5-HT3-antagonist attenuated the hypotensive (10%), bradycardiac (1.7%), tachypnoeic (11%) and hyperventilatory (11%) responses significantly. Pretreatment with capsazepine (1 mg/kg), transient receptor potential vanilloid 1- antagonist blocked the hypotensive (5%), bradycardiac (1.2%), tachypnoeic (6%) and hyperventilatory (6%) responses significantly. Conclusion: In conclusion, presence of a nociceptive agent in the local segment of an artery evokes vasosensory reflex responses modulating CVR parameters involving TRPV1 and 5-HT3 receptors present on the perivascular sensory nerve terminals in anesthetized rats.

Protein kinase C potentiates cAMP-stimulated mouse duodenal mucosal bicarbonate secretion in vitro

2004 ◽  
Vol 286 (5) ◽  
pp. G814-G821 ◽  
Author(s):  
Bi-Guang Tuo ◽  
Jimmy Y. C. Chow ◽  
Kim E. Barrett ◽  
Jon I. Isenberg
Keyword(s):  
Short Circuit ◽  
Short Circuit Current ◽  
Duodenal Mucosa ◽  
Bicarbonate Secretion ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Ussing Chambers ◽  
Duodenal Bicarbonate Secretion

PKC has been shown to regulate epithelial Cl- secretion in a variety of models. However, the role of PKC in duodenal mucosal bicarbonate secretion is less clear. We aimed to investigate the role of PKC in regulation of duodenal mucosal bicarbonate secretion. Bicarbonate secretion by murine duodenal mucosa was examined in vitro in Ussing chambers using a pH-stat technique. PKC isoform expression and activity were assessed by Western blotting and in vitro kinase assays, respectively. PMA (an activator of PKC) alone had no effect on duodenal bicarbonate secretion or short-circuit current ( Isc). When PMA and dibutyryl-cAMP (db-cAMP) were added simultaneously, PMA failed to alter db-cAMP-stimulated duodenal bicarbonate secretion or Isc ( P > 0.05). However, a 1-h preincubation with PMA potentiated db-cAMP-stimulated duodenal bicarbonate secretion and Isc in a concentration-dependent manner (from 10-8 to 10-5M) ( P < 0.05). PMA preincubation had no effects on carbachol- or heat-stable toxin-stimulated bicarbonate secretion. Western blot analysis revealed that PKCα, -γ, -ϵ, -θ, -μ, and -ι/λ were expressed in murine duodenal mucosa. Ro 31–8220 (an inhibitor active against PKCϵ, -α, -β, and -γ), but not Gö 6983 (an inhibitor active against PKCα, -γ, -β, and -δ), reversed the potentiating effect of PMA on db-cAMP-stimulated bicarbonate secretion. PMA also time- and concentration-dependently increased the activity of PKCϵ, an effect that was prevented by Ro 31–8220 but not Gö 6983. These results demonstrate that activation of PKC potentiates cAMP-stimulated duodenal bicarbonate secretion, whereas it does not modify basal secretion. The effect of PKC on cAMP-stimulated bicarbonate secretion is mediated by the PKCϵ isoform.

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