scholarly journals Calcium controls smooth muscle TRPC gene transcription via the CaMK/calcineurin-dependent pathways

2007 ◽  
Vol 292 (1) ◽  
pp. C553-C563 ◽  
Author(s):  
Sara Morales ◽  
Amalia Diez ◽  
Antonio Puyet ◽  
Pedro J. Camello ◽  
Cristina Camello-Almaraz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Smooth Muscle ◽  
Protein Expression ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Camp Response Element Binding ◽  
Gene And Protein Expression ◽  
Element Binding Protein ◽  
Transient Receptor ◽  
Trpc Gene

Transient receptor potential protein family C (TRPC) has been proposed as a candidate for channels involved in capacitative Ca2+ entry (CCE) mechanisms, but the modulation of their gene expression remains unexplored. In this study we show that guinea pig gallbladder smooth muscle contains mRNA encoding TRPC1, TRPC2, TRPC3, and TRPC4 proteins whose abundance depends on cytosolic Ca2+ level ([Ca2+]i). Thus lowering the levels of cellular calcium with the chelators EGTA and BAPTA AM results in a downregulation of TRPC1–TRPC4 gene and protein expression. In contrast, activation of Ca2+ influx through L-type Ca2+ channels and Ca2+ release from intracellular stores induced an increase in TRPC1–TRPC4 mRNA and protein abundance. Activation of Ca2+/calmodulin-dependent kinases (CaMK) and phosphorylation of cAMP-response element binding protein accounts for the increase in TRPC mRNA transcription in response to L-type channel-mediated Ca2+ influx . In addition to this mechanism, activation of TRPC gene expression by intracellular Ca2+ release also involves calcineurin pathway. According to the proposed role for these channels, activation of CCE induced an increase in TRPC1 and TRPC3 mRNA abundance, which depends on the integrity of the calcineurin and CaMK pathways. These findings show for the first time an essential autoregulatory role of Ca2+ in Ca2+ homeostasis at the level of TRPC gene and protein expression.

scholarly journals The Transient Receptor Potential Vanilloid 1 Is Associated with Active Inflammation in Ulcerative Colitis

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Joel Jesús Toledo-Mauriño ◽  
Janette Furuzawa-Carballeda ◽  
Marco A. Villeda-Ramírez ◽  
Gabriela Fonseca-Camarillo ◽  
Daniela Meza-Guillen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ulcerative Colitis ◽  
Protein Expression ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Rt Pcr ◽  
Gene And Protein Expression ◽  
Transient Receptor ◽  
Active Inflammation

The transient receptor potential vanilloid 1 (TRPV1) may play a role in the pathogenesis of ulcerative colitis (UC). The aim of the study was to determine the gene and protein expression of TRPV1 in UC patients and noninflamed controls. Gene expression was performed by RT-PCR, and protein expression was performed by immunohistochemistry. The gene expression of TRPV1 was significantly increased in the remission UC group compared to active UC patients (P=0.002), and an upregulation of the TRPV1 gene was associated with clinical outcomes such as age at diagnosis (<40 years) (P=0.02) and clinical disease course characterized by relapsing and continuous activity (P=0.07). TRPV1 immunoreactive cells were conspicuously higher in all intestinal layers from active UC patients compared with noninflamed control tissue. These findings suggest that TRPV1 might be involved in UC pathogenesis.

Enhanced capacitative calcium entry and TRPC channel gene expression in human LES smooth muscle

2003 ◽  
Vol 284 (6) ◽  
pp. G1074-G1083 ◽  
Author(s):  
Jian Wang ◽  
Lisanne G. Laurier ◽  
Stephen M. Sims ◽  
Harold G. Preiksaitis
Keyword(s):  
Gene Expression ◽  
Smooth Muscle ◽  
Transient Receptor Potential ◽  
Smooth Muscles ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
Transcriptional Expression ◽  
External Application ◽  
Intracellular Ca ◽  
Transient Receptor

Transient receptor potential channel ( TRPC) genes encode Ca2+-permeable channels mediating capacitative Ca2+ entry (CCE), which maintains intracellular Ca2+ stores. We compared TRPC gene expression and CCE in human esophageal body (EB) and lower esophageal sphincter (LES), because these smooth muscles have distinct contractile functions that are likely associated with different Ca2+ regulatory mechanisms. Circular layer smooth muscle cells were grown in primary culture. Transcriptional expression of TRPC genes was compared by semiquantitative RT-PCR. CCE was measured by fura 2 Ca2+ fluorescence after blockade of sarcoplasmic reticulum Ca2+-ATPase with thapsigargin. mRNA for TRPC1, TRPC3, TRPC4, TRPC5, and TRPC6was identified in EB and LES. TRPC3 and TRPC4were more abundant in LES than EB. Basal concentration of free intracellular Ca2+ ([Ca2+]i) was similar in cells from LES (138 ± 8 nmol/l) and EB (110 ± 6 nmol/l) and increased with ACh (10 μmol/l; 650 ± 28 and 590 ± 21 nmol/l, respectively). With zero Ca2+ in bath, thapsigargin (2 μmol/l) increased [Ca2+]i more in LES (550 ± 22 nmol/l) than EB (250 ± 15 nmol/l, P < 0.001). Subsequent external application of 1 mmol/l Ca2+ increased [Ca2+]i more in LES (585 ± 35 nmol/l) than EB (295 ± 21 nmol/l, P < 0.001), indicating enhanced CCE in LES. This demonstrates CCE and TRPC transcriptional expression in human esophageal smooth muscle. In LES cells, enhanced CCE and expression of TRPC3 and TRPC4 may contribute to the physiological characteristics that distinguish LES from EB.

scholarly journals Analysis of transient receptor potential vanilloid 1 and substance P gene expression in the mouse tongue following oral ginger administration

2016 ◽  
Vol 5 (4) ◽  
pp. 131-134
Author(s):  
Iizuka Michiro ◽  
◽  
Hirata Ayumu ◽  
Abe Noriaki ◽  
Jobu Kohei ◽  
...  
Keyword(s):  
Gene Expression ◽  
Substance P ◽  
Protein Expression ◽  
Mrna Expression ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
P Gene ◽  
Glandular Cells ◽  
Transient Receptor

Ginger rhizome (Zingiber officinale) exhibits multiple pharmacological actions. For example, its pungent components target the transient receptor potential vanilloid 1 (TRPV1) ion channel and thus contribute to swallowing reflex recovery by elevating the neuropeptide substance P. However, the precise mechanism underlying this action remains unclear. To examine TRPV1 and substance P gene expression in the mouse tongue in response to stimulation by orally administered ginger, quantitative real-time polymerase chain reaction and immunohistochemistry were performed to evaluate mRNA and protein expression. TRPV1 mRNA expression in the mouse tongue was upregulated 30 min after oral ginger stimulation. In the gingerstimulated mouse, TRPV1 protein expression was increased and concentrated in the plasma membranes of the mucous glandular cells of the tongue epithelium. No significant differences in substance P mRNA expression relative to the control were observed after ginger stimulation. However, immunohistochemistry revealed that the amount of substance P protein expression increased in the mucous glandular cells of the tongue epithelium in ginger-stimulated mice, and this expression appeared to concentrate in the secretory granules of these cells. Activation of TRPV1 promotes the secretion of substance P in saliva, and clinically, saliva levels of substance P can be measured noninvasively and can provide a useful biomarker of the swallowing function. An increased level of substance P in the saliva could indicate improved dysphagia. Our data suggest that ginger activates TRPV1 and promotes the secretion of substance P in saliva. Ginger is therefore expected to serve as a functional agent for improving dysphagia.

scholarly journals Novel Mechanistic Insights and Potential Therapeutic Impact of TRPC6 in Neurovascular Coupling and Ischemic Stroke

2021 ◽  
Author(s):  
Shashank Shekhar ◽  
Yedan Liu ◽  
Shaoxun Wang ◽  
Huawei Zhang ◽  
Xing Fang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Transient Receptor Potential ◽  
Glutamate Release ◽  
Neurovascular Coupling ◽  
Receptor Potential ◽  
Camp Response Element Binding ◽  
Element Binding Protein ◽  
Excitotoxic Damage ◽  
Transient Receptor ◽  
The Brain

Ischemic stroke is one of the most disabling diseases and a leading cause of death globally. Despite advances in medical care, the global burden of stroke continues to grow, as no effective treatments to limit or reverse ischemic injury to the brain are available. However, recent preclinical findings have revealed the potential role of transient receptor potential cation 6 (TRPC6) channels as endogenous protectors of neuronal tissue. Activating TRPC6 in various cerebral ischemia models has been found to prevent neuronal death, whereas blocking TRPC6 enhances sensitivity to ischemia. Evidence has shown that Ca2+ influx through TRPC6 activates cAMP response element-binding protein (CREB), an important transcription factor linked to neuronal survival. Additionally, TRPC6 activation may counter excitotoxic damage resulting from glutamate release by attenuating the activity of NMDA receptors of neurons by posttranslational means. Unresolved though, are the roles of TRPC6 channels in non-neuronal cells such as astrocytes and endothelial cells. Moreover, TRPC6 channels may have detrimental effects on the blood-brain barrier, although their exact role in neurovascular coupling requires further investigation. This review discusses evidence-based cell-specific aspects of TRPC6 in the brain to assess the potential targets for ischemic stroke management.

Role of capacitative Ca2+ entry in bronchial contraction and remodeling

2002 ◽  
Vol 92 (4) ◽  
pp. 1594-1602 ◽  
Author(s):  
Michele Sweeney ◽  
Sharon S. McDaniel ◽  
Oleksandr Platoshyn ◽  
Shen Zhang ◽  
Ying Yu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Transient Receptor Potential ◽  
Bronchial Hyperresponsiveness ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
Wall Thickening ◽  
Bronchial Wall ◽  
Intracellular Ca ◽  
Transient Receptor

Asthma is characterized by airway inflammation, bronchial hyperresponsiveness, and airway obstruction by bronchospasm and bronchial wall thickening due to smooth muscle hypertrophy. A rise in cytosolic free Ca2+ concentration ([Ca2+]cyt) may serve as a shared signal transduction element that causes bronchial constriction and bronchial wall thickening in asthma. In this study, we examined whether capacitative Ca2+ entry (CCE) induced by depletion of intracellular Ca2+ stores was involved in agonist-mediated bronchial constriction and bronchial smooth muscle cell (BSMC) proliferation. In isolated bronchial rings, acetylcholine (ACh) induced a transient contraction in the absence of extracellular Ca2+ because of Ca2+ release from intracellular Ca2+ stores. Restoration of extracellular Ca2+in the presence of atropine, an M-receptor blocker, induced a further contraction that was apparently caused by a rise in [Ca2+]cyt due to CCE. In single BSMC, amplitudes of the store depletion-activated currents ( I SOC) and CCE were both enhanced when the cells proliferate, whereas chelation of extracellular Ca2+ with EGTA significantly inhibited the cell growth in the presence of serum. Furthermore, the mRNA expression of TRPC1, a transient receptor potential channel gene, was much greater in proliferating BSMC than in growth-arrested cells. Blockade of the store-operated Ca2+channels by Ni2+ decreased I SOC and CCE and markedly attenuated BSMC proliferation. These results suggest that upregulated TRPC1 expression, increased I SOC, enhanced CCE, and elevated [Ca2+]cyt may play important roles in mediating bronchial constriction and BSMC proliferation.

scholarly journals A comprehensive analysis of vomeronasal organ transcriptome reveals variable gene expression depending on age and function in rabbits

2020 ◽  
Author(s):  
PR Villamayor ◽  
D Robledo ◽  
C Fernández ◽  
J Gullón ◽  
L Quintela ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transient Receptor Potential ◽  
Expression Patterns ◽  
Vomeronasal Organ ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
List Type ◽  
Gene Repertoire ◽  
Behavioural Responses ◽  
Transient Receptor

ABSTRACTThe vomeronasal organ (VNO) is a chemosensory organ specialized in the detection of pheromones and consequently the regulation of behavioural responses mostly related to reproduction. VNO shows a broad variation on its organization, functionality and gene expression in vertebrates, and although the species analyzed to date have shown very specific features, its expression patterns have only been well-characterized in mice. Despite rabbits represent a model of chemocommunication, unfortunately no genomic studies have been performed on VNO of this species to date. The capacity of VNO to detect a great variety of different stimuli suggests a large number of genes with complex organization to support this function. Here we provide the first comprehensive gene expression analysis of the rabbit VNO through RNA-seq across different sexual maturation stages. We characterized the VNO transcriptome, updating the number of the two main vomeronasal receptor (VR) families, 129 V1R and 70 V2R. Among others, the expression of transient receptor potential channel 2 (TRPC2), a crucial cation channel generating electrical responses to sensory stimulation in vomeronasal neurons, along with the specific expression of some fomyl-peptide receptors and H2-Mv genes, both known to have specific roles in the VNO, revealed a the particular gene expression repertoire of this organ, but also its singularity in rabbits. Moreover, juvenile and adult VNO transcriptome showed consistent differences, which may indicate that these receptors are tuned to fulfill specific functions depending on maturation age. We also identified VNO-specific genes, including most VR and TRPC2, thus confirming their functional association with the VNO. Overall, these results represent the genomic baseline for future investigations which seek to understand the genetic basis of behavioural responses canalized through the VNO.HIGHLIGHTSFirst description of the rabbit vomeronasal organ (VNO) transcriptomeVNO contains a unique gene repertoire depending on the speciesHigh fluctuation of the VNO gene expression reveals changes dependent on age and specific functionsMost vomeronasal-receptors (VR) and transient receptor potential channel 2 (TRPC2) genes are VNO-specificReproduction-related genes shows a wide expression pattern

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