scholarly journals Differential regulation of TRPC4 in the vasopressin magnocellular system by water deprivation and hepatic cirrhosis in the rat

2014 ◽  
Vol 306 (5) ◽  
pp. R304-R314 ◽  
Author(s):  
T. Prashant Nedungadi ◽  
J. Thomas Cunningham
Keyword(s):  
Protein Expression ◽  
Water Deprivation ◽  
Hepatic Cirrhosis ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Vasopressin Release ◽  
Duct Ligation ◽  
Channel Expression ◽  
Transient Receptor ◽  
Laser Capture

Transient receptor potential canonical subtype 4 (TRPC4) is expressed in the magnocellular paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus. In this study, the regulation of TRPC4 expression was investigated in water deprivation and hepatic cirrhosis. We used laser capture microdissection technique for precise dissection of pure AVP cell population in the PVN and SON followed by quantitative real-time RT-PCR, and immunodetection techniques by Western blot analysis and immunofluorescence. Bile duct ligation elevated TRPC4 transcripts in the SON but not PVN with correlated changes in the protein expression in these regions, as well as increased colocalization with AVP in the SON, with no changes in the PVN. Water deprivation resulted in increased TRPC4 mRNA expression in the PVN, while it decreased channel expression levels in the SON. In both of these regions, protein expression measured from tissue punches were unaltered following water deprivation, with no changes in the number of TRPC4-positive cells. Thus, TRPC4 expression is differentially regulated in physiological and pathophysiological models of vasopressin release.

scholarly journals Vasopressin at Central Levels and Consequences of Dehydration

2016 ◽  
Vol 68 (Suppl. 2) ◽  
pp. 19-23 ◽  
Author(s):  
Daniel G. Bichet
Keyword(s):  
Animal Studies ◽  
Transient Receptor Potential ◽  
Animal Experiments ◽  
Extracellular Fluid ◽  
Receptor Potential ◽  
Circumventricular Organ ◽  
Thermal Perception ◽  
Trpv1 Channel ◽  
Vasopressin Release ◽  
Transient Receptor

Disorders of water balance are a common feature of clinical practice. An understanding of the physiology and pathophysiology of central vasopressin release and perception of thirst is the key to diagnosis and management of these disorders. Mammals are osmoregulators; they have evolved mechanisms that maintain extracellular fluid osmolality near a stable value, and, in animal studies, osmoregulatory neurons express a truncated delta-N variant of the transient receptor potential vannilloid (TRPV1) channel involved in hypertonicity and thermal perception while systemic hypotonicity might be perceived by TRPV4 channels. Recent cellular and optogenetic animal experiments demonstrate that, in addition to the multifactorial process of excretion, circumventricular organ sensors reacting to osmotic pressure and angiotensin II, subserve genesis of thirst, volume regulation and behavioral effects of thirst avoidance.

scholarly journals Human transient receptor potential (TRP) channel expression profiling in carcinogenesis

2015 ◽  
Vol 59 (7-8-9) ◽  
pp. 399-406 ◽  
Author(s):  
Michela Bernardini ◽  
Alessandra Fiorio Pla ◽  
Natalia Prevarskaya ◽  
Dimitra Gkika
Keyword(s):  
Expression Profiling ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Trp Channel ◽  
Channel Expression ◽  
Transient Receptor

Mibefradil suppresses the proliferation of pulmonary artery smooth muscle cells

2016 ◽  
Vol 64 (1) ◽  
pp. 45-49 ◽  
Author(s):  
Hong-Hong Li ◽  
Li-Jian Xie ◽  
Ting-Ting Xiao ◽  
Min Huang ◽  
Jie Shen
Keyword(s):  
Smooth Muscle ◽  
Pulmonary Artery ◽  
Transient Receptor Potential ◽  
Critical Role ◽  
Receptor Potential ◽  
Channel Expression ◽  
Intracellular Ca ◽  
Pulmonary Arterial ◽  
Pulmonary Artery Smooth Muscle ◽  
Transient Receptor

Intracellular Ca2+ levels play a critical role in the regulation of vasodilation and vasoconstriction by stimulating pulmonary artery smooth muscle cell (PASMC) proliferation, which is important in the pathogenesis of pulmonary arterial hypertension (PAH); however, L-type Ca2+ channel antagonists are useful in only few patients with PAH. The present study sought to assess the effect of mibefradil, which blocks T-type Ca2+ channels, on PASMC proliferation and Ca2+ channel profile. Human PASMCs were stimulated with 25 ng/mL platelet-derived growth factor-BB (PDGF-BB) with and without 10 µM mibefradil or 100 nM sildenafil. After 48 or 72 h, PASMC proliferation and Ca2+ channel expression were assessed by MTT assays and western blot analysis, respectively. PDGF-BB-induced PASMC proliferation at 72 h (p<0.01), which was inhibited by both sildenafil and mibefradil (p<0.01). Transient receptor potential Ca2+ channel 6 (TRPC6) expression was significantly increased with PDGF-BB stimulation (p=0.009); however, no changes in TRPC1, TRPC3, CAV1.2, and CAV3.2 levels were observed. Although both TRPC1 and CAV1.2 expression levels were increased in PDGF-stimulated PASMCs on mibefradil and sildenafil treatment, it was not statistically significant (p=0.086 and 1.000, respectively). Mibefradil inhibits PDGF-BB-stimulated PASMC proliferation; however, the mechanism through which it functions remains to be determined. Further studies are required to elucidate the full therapeutic value of mibefradil for PAH.

scholarly journals Enhanced store-operated Ca2+ entry and TRPC channel expression in pulmonary arteries of monocrotaline-induced pulmonary hypertensive rats

2012 ◽  
Vol 302 (1) ◽  
pp. C77-C87 ◽  
Author(s):  
Xiao-Ru Liu ◽  
Ming-Fang Zhang ◽  
Na Yang ◽  
Qing Liu ◽  
Rui-Xing Wang ◽  
...  
Keyword(s):  
Time Course ◽  
Vascular Reactivity ◽  
Transient Receptor Potential ◽  
Pulmonary Arteries ◽  
Cyclopiazonic Acid ◽  
Receptor Potential ◽  
Treated Group ◽  
Channel Expression ◽  
Pulmonary Arterial ◽  
Transient Receptor

Pulmonary hypertension (PH) is associated with profound vascular remodeling and alterations in Ca2+ homeostasis in pulmonary arterial smooth muscle cells (PASMCs). Previous studies show that canonical transient receptor potential (TRPC) genes are upregulated and store-operated Ca2+ entry (SOCE) is augmented in PASMCs of chronic hypoxic rats and patients of pulmonary arterial hypertension (PAH). Here we further examine the involvement of TRPC and SOCE in PH with a widely used rat model of monocrotaline (MCT)-induced PAH. Rats developed severe PAH, right ventricular hypertrophy, and significant increase in store-operated TRPC1 and TRPC4 mRNA and protein in endothelium-denuded pulmonary arteries (PAs) 3 wk after MCT injection. Contraction of PA and Ca2+ influx in PASMC evoked by store depletion using cyclopiazonic acid (CPA) were enhanced dramatically, consistent with augmented SOCE in the MCT-treated group. The time course of increase in CPA-induced contraction corresponded to that of TRPC1 expression. Endothelin-1 (ET-1)-induced vasoconstriction was also potentiated in PAs of MCT-treated rats. The response was partially inhibited by SOCE blockers, including Gd3+, La3+, and SKF-96365, as well as the general TRPC inhibitor BTP-2, suggesting that TRPC-dependent SOCE was involved. Moreover, the ET-1-induced contraction and Ca2+ response in the MCT group were more susceptible to the inhibition caused by the various SOCE blockers. Hence, our study shows that MCT-induced PAH is associated with increased TRPC expression and SOCE, which are involved in the enhanced vascular reactivity to ET-1, and support the hypothesis that TRPC-dependent SOCE is an important pathway for the development of PH.

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