Molecular and functional characterization of TRPV4 channels in pregnant and nonpregnant mouse uterus

Singh, Vishal; Ram, Mahendra; Kandasamy, Kannan; Thangamalai, Ramasamy; Choudhary, Soumen; Dash, Jeevan Ranjan; Kumar, Dhirendra; Parida, Subhashree; Singh, Thakur Uttam; Mishra, Santosh Kumar

doi:10.1016/j.lfs.2014.12.010

Cited by 28 publications

(21 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This indicates that they might play a role in estrogen-evoked signal generation and transmission in conditions with altered sex hormone levels. Similarly to other TRP or cation channels of the endometrium (Ruan et al 2014, Singh et al 2015, TRPA1/TRPV1 may mediate homeostatic and barrier functions, Ca 2C signalling, cell proliferation/differentiation, endometrial receptivity, embryo implantation and sensory-immune interactions (Fernandes et al 2012). Non-neuronal TRPV1 can also be activated by the endocannabinoid anandamide in the rat reproductive system (Cella et al 2008, Scotchie et al 2014.…”

Section: Discussionmentioning

confidence: 99%

Estrogen-dependent up-regulation of TRPA1 and TRPV1 receptor proteins in the rat endometrium

Pohóczky

Kun

Szalontai

et al. 2015

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

Transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) receptors expressed predominantly in sensory nerves are activated by inflammatory stimuli and mediate inflammation and pain. Although they have been shown in the human endometrium, their regulation and function are unknown. Therefore, we investigated their estrogen-and progesterone-dependent alterations in the rat endometrium in comparison with the estrogenregulated inflammatory cytokine macrophage migration inhibitory factor (MIF). Four-week-old (sexually immature) and four-month-old (sexually mature) female rats were treated with the non-selective estrogen receptor (ER) agonist diethylstilboestrol (DES), progesterone and their combination, or ovariectomized. RT-PCR and immunohistochemistry were performed to determine mRNA and protein expression levels respectively. Channel function was investigated with ratiometric [Ca 2C ] i measurement in cultured primary rat endometrial cells. Both TRP receptors and MIF were detected in the endometrium at mRNA and protein levels, and their localizations were similar. Immunostaining was observed in the immature epithelium, while stromal, glandular and epithelial positivity were observed in adults. Functionally active TRP receptor proteins were shown in endometrial cells by activation-induced calcium influx. In adults, Trpa1 and Trpv1 mRNA levels were significantly up-regulated after DES treatment. TRPA1 increased after every treatment, but TRPV1 remained unchanged following the combined treatment and ovariectomy. In immature rats, DES treatment resulted in increased mRNA expression of both channels and elevated TRPV1 immunopositivity. MIF expression changed in parallel with TRPA1/TRPV1 in most cases. DES up-regulated Trpa1, Trpv1 and Mif mRNA levels in endometrial cell cultures, but 17b-oestradiol having ERa-selective potency increased only the expression of Trpv1. We provide the first evidence for TRPA1/TRPV1 expression and their estrogen-induced up-regulation in the rat endometrium in correlation with the MIF. Journal of Molecular EndocrinologyResearch K POHÓ CZKY and others TRPV1 and TRPA1 in the rat endometrium 56:2 135-149

show abstract

Section: Discussionmentioning

confidence: 99%

Estrogen-dependent up-regulation of TRPA1 and TRPV1 receptor proteins in the rat endometrium

Pohóczky

Kun

Szalontai

et al. 2015

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

show abstract

“…The putative role of another calcium conductance supported by TRPV4 channels was also assessed, the latter having previously been shown to be involved in the control of other smooth muscle reactivity, mainly from the vascular bed [8,12,13,27]. The pharmacology of such conductance has moreover yielded the synthesis of a new agonist and antagonist [28]. Thus, the effect of the TRPV4 agonist GSK1016790A and TRPVA antagonist HC-067047 were tested on oxytocin-induced contractions.…”

Section: Involvement Of Trpv4 In the Control Of Human Myometrial Contmentioning

confidence: 99%

Involvement of Alternative Calcium Conductance on Human Myometrial Contractile and Pharmacological Properties

Rousseau

Labelle

Massenavette

2018

COGO

View full text Add to dashboard Cite

Objective: This study aimed to investigate the physiological role of alternative calcium conduct once contractions triggered by oxytocin and PGF2α in human myometrium. This conductance, supported by TRPC and TRPV channels, may provide alternative pathways to control either free intracellular and/or submembrane Ca 2+ -concentrations, which in turn will modulate membrane polarization and contractile responses. Study design:Uterine biopsies were obtained from consenting women undergoing elective caesarian delivery at term without labor (N = 29). Isometric tension measurements were performed on uterine strips (n = 174). Amplitudes, frequencies and areas under the curve (AUC) of phasic contractions as well as resting tone were measured under various experimental conditions. Norgestimate, which has been shown to inhibit TRPC isoforms, was added to isolated organ baths to delineate their putative functional involvement. In order to assess the role of TRPV4 channels, rhythmic activity triggered by uterotonic drugs was determined in the absence and presence of either 1 μM HC-067047 (TRPV4 antagonist) or 100 nM GSK1016790A (TRPV4 agonist). Addition of 50 nM iberiotoxin (IbTX) as well as of 10 µM NS-1619 was also used to assess the involvement of GKCa channels in controlling uterine reactivity and contractility.Results: Micromolar concentrations of norgestimate consistently decreased the resting tone, frequency and maximal amplitude of oxytocin -and PGF2α -induced contractions. In contrast, the TRPV4 agonist GSK1016790A abolished the rhythmic contractions, resulting in a strong and reversible tocolytic effect. Addition of iberiotoxin (a GKCa blocker) reversed the effects of GSK1016790A, while NS1619 mimicked the rapid tocolytic effects of the TRPV4 agonist. Conclusion:Acute pharmacological inhibition of TRPC channels by norgestimate had minor effects on contractile parameters although resting -tone was lowered. In contrast, selectiveTRPV4 activation led to GKCa activation, which in turn hyperpolarized the myometrial cell membrane, inactivating Ca 2+ channels and efficiently abrogated contractile activity. Collectively, these data suggest that alternative calcium conduct ance may play a physiological role in the modulation of myometrial reactivity prior to delivery. A rapid switch from phasic contractions to quiescence by this new class of tocolytics may potentially be of interest in delaying parturition in preterm labor.

show abstract

“…To assess any effect of high cholesterol on the voltage-gated Ca 2+ channel, concentration-response curve to CaCl 2 was elicited after equilibration of uterine tissue in Ca 2+ free 40 mM KCl for 30 min in uterine strips of control mice and compared with high cholesterol group uterine tissue. The detailed protocol for this experiment has been described elsewhere (Singh et al 2015).…”

Section: Assessment Of the Effect Of Hypercholesterolemia On Cacl 2 -mentioning

confidence: 99%

Hypercholesterolemia impairs oxytocin-induced uterine contractility in late pregnant mouse

Padol¹,

Sukumaran²,

Sadam³

et al. 2017

Reproduction

Self Cite

View full text Add to dashboard Cite

High cholesterol is known to negatively affect uterine contractility in conditions. The aim of the present study was to reveal the effect of hypercholesterolemia on spontaneous and oxytocin-induced uterine contractility in late pregnant mouse uterus. Female Swiss albino mice were fed with high cholesterol (HC) diet (0.5% sodium cholate, 1.25% cholesterol and 15% fat) for 6 weeks and then throughout the gestation period after mating. On day 19 of gestation, serum cholesterol level was increased more than 3-fold while triglycerides level was reduced in HC diet-fed animals as compared to control animals fed with a standard diet. In tension experiments, neither the mean integral tension of spontaneous contractility nor the response to CaCl in high K-depolarized tissues was altered, but the oxytocin-induced concentration-dependent contractile response in uterine strips was attenuated in hypercholesterolemic mice as compared to control. Similarly, hypercholesterolemia dampened concentration-dependent uterine contractions elicited by a GNAQ protein activator, toxin. However, it had no effect on endogenous oxytocin level either in plasma or in uterine tissue. It also did not affect the prostaglandin release in oxytocin-stimulated tissues. Western blot data showed a significant increase in caveolin-1 and GRK6 proteins but decline in oxytocin receptor, GNAQ and RHOA protein expressions in hypercholesterolemic mouse uterus. The results of the present study suggest that hypercholesterolemia may attenuate the uterotonic action of oxytocin in late pregnancy by causing downregulation of oxytocin receptors and suppressing the signaling efficacy through GNAQ and RHOA proteins.

show abstract

Molecular and functional characterization of TRPV4 channels in pregnant and nonpregnant mouse uterus

Cited by 28 publications

References 36 publications

Estrogen-dependent up-regulation of TRPA1 and TRPV1 receptor proteins in the rat endometrium

Estrogen-dependent up-regulation of TRPA1 and TRPV1 receptor proteins in the rat endometrium

Involvement of Alternative Calcium Conductance on Human Myometrial Contractile and Pharmacological Properties

Hypercholesterolemia impairs oxytocin-induced uterine contractility in late pregnant mouse

Contact Info

Product

Resources

About