scholarly journals The Role of Two-Pore Channels in Norepinephrine-Induced [Ca2+]i Rise in Rat Aortic Smooth Muscle Cells and Aorta Contraction

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1144 ◽  
Author(s):  
Sergei K. Trufanov ◽  
Elena Yu. Rybakova ◽  
Piotr P. Avdonin ◽  
Alexandra A. Tsitrina ◽  
Irina L. Zharkikh ◽  
...  

Second messenger nicotinic acid adenine dinucleotide phosphate (NAADP) triggers Ca2+ release via two-pore channels (TPCs) localized in endolysosomal vesicles. The aim of the present work is to evaluate the role of TPCs in the action of norepinephrine (NE), angiotensin II (AngII), vasopressin (AVP), and 5-hydroxytriptamine (5-HT) on free cytoplasmic calcium concentration ([Ca2+]i) in smooth muscle cells (SMCs) isolated from rat aorta and on aorta contraction. To address this issue, the NAADP structural analogue and inhibitor of TPCs, NED 19, was applied. We have demonstrated a high degree of colocalization of the fluorescent signals of cis-NED 19 and endolysosmal probe LysoTracker in SMCs. Both cis- or trans-NED 19 inhibited the rise of [Ca2+]i in SMCs induced by 100 μM NE by 50–60%. IC50 for cis- and trans-NED 19 were 2.7 and 8.9 μM, respectively. The inhibition by NED 19 stereoisomers of the effects of AngII, AVP, and 5-HT was much weaker. Both forms of NED 19 caused relaxation of aortic rings preconstricted by NE, with relative potency of cis-NED 19 several times higher than that of trans-NED 19. Inhibition by cis-NED 19 of NE-induced contraction was maintained after intensive washing and slowly reversed within an hour of incubation. Cis- and trans-NED 19 did not cause decrease in the force of aorta contraction in response to Ang II and AVP, and only slightly relaxed aorta preconstricted by 5-HT and by KCl. Suppression of TPC1 in SMCs with siRNA caused a 40% decrease in [Ca2+]i in response to NE, whereas siRNA against TPC2 did not change NE calcium signaling. These data suggest that TPC1 is involved in the NE-stimulated [Ca2+]i rise in SMCs. Inhibition of TPC1 activity by NED 19 could be the reason for partial inhibition of aortic rings contraction in response to NE.

Science ◽  
1986 ◽  
Vol 232 (4746) ◽  
pp. 87-90 ◽  
Author(s):  
BC Berk ◽  
RW Alexander ◽  
TA Brock ◽  
MA Gimbrone ◽  
RC Webb

Platelet-derived growth factor (PDGF) is a potent mitogen for vascular smooth muscle cells that has been implicated in the pathogenesis of atherosclerosis. The potential role of PDGF in the altered vasoreactivity of atherosclerotic vessels has been studied through an examination of its effects on contractility in the rat aorta. PDGF caused a concentration-dependent contraction of aortic strips and was significantly more potent on a molar basis than the classic vasoconstrictor peptide angiotensin II. Furthermore, PDGF increased the cytosolic free calcium concentration in cultured rat aortic smooth muscle cells. These observations suggest a new biological activity for PDGF that may contribute to the enhanced vasoreactivity of certain atherosclerotic vessels.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Wenhui Gao ◽  
Rong Li ◽  
Jingjing Yu ◽  
Xijie He ◽  
Duo Xu ◽  
...  

Abstract Background SCIRT has been characterized as a key player in cancer biology, while its role in other human diseases is unclear. This study explored its role in atherosclerosis, with a specific focus on its interaction with SCIRT and miR-146a. Methods The expression of SCIRT and miR-146a in atherosclerosis-affected tissues and healthy tissues from 56 atherosclerosis patients were analyzed by RT-qPCR. The expression of SCIRT in nuclear and cytoplasm samples was detected by RNA fractionation assay. The direct interaction between SCIRT and miR-146a was detected by RNA pull-down assay. SCIRT and miR-146a were overexpressed in human aortic smooth muscle cells (HAOSMCs) to study the crosstalk between them. The role of SCIRT and miR-146a in the proliferation of HAOSMCs was analyzed with BrdU assay. Results SCIRT was downregulated by atherosclerosis, while miR-146a was upregulated by atherosclerosis. SCIRT was detected in both cytoplasm and nuclear samples, and it directly interacted with miR-146a. In HAOSMCs, overexpression of SCIRT and miR-146a did not affect the expression of each other. Interestingly, SCIRT suppressed the proliferation of HAOSMCs and reduced the enhancing effects of miR-146a on cell proliferation. Conclusion Therefore, SCIRT is downregulated in atherosclerosis and it suppresses the proliferation of HAOSMCs by sponging miR-146a in cytoplasm.


2009 ◽  
Vol 8 (4) ◽  
pp. 41-46
Author(s):  
I. V. Kovalyev ◽  
S. V. Gusakova ◽  
O. S. Melnik ◽  
M. B. Baskakov ◽  
L. V. Kapilevich ◽  
...  

The influence of of hydrogen peroxide on the contractile reactions of smooth muscle cells caused by hyperpotassium solution end phenylephrine in modulation a potassium conductance the membrane and the state of cytoskeleton elements has been investigated by the mechanographical method. It has multidirectional influence of hydrogen peroxide in the reduction of smooth muscles of rat aorta with the membrane depolarization hyperpotassium solution and action phenylephrine: phenylephrine decline in value and increase strength hyperpotassium contractures. We show that the cytoskeleton components involved in the mechanisms of action of hydrogen peroxide in the contractile reactions of smooth muscles of rat aorta caused by phenylephrine.


2008 ◽  
Vol 49 (3-4) ◽  
pp. 189-192 ◽  
Author(s):  
Davide Vigetti ◽  
Paola Moretto ◽  
Manuela Viola ◽  
Anna Genasetti ◽  
Manuela Rizzi ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document