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dc.contributor.authorTrufanov, S. K.
dc.contributor.authorRybakova, E. Y.
dc.contributor.authorAvdonin, P. P.
dc.contributor.authorTSITRINA, A. A.
dc.contributor.authorGoncharov, N. V.
dc.contributor.authorJenkins, R. O.
dc.contributor.authorAvdonin, P. V.
dc.date.accessioned2019-09-26T10:34:06Z
dc.date.available2019-09-26T10:34:06Z
dc.date.issued2019-09-25
dc.identifier.citationTRUFANOV S. K., RYBAKOVA E. Y., AVDONIN P.P., TSITRINA A.A.,ZHARKIKH I.L.,GONCHAROV N.V., JENKINS R.O., AVDONIN P.V. The role of two-pore channels in norepinephrine-induced [Ca2+]i rise in rat aortic smooth muscle cells and aorta contraction. Cells, 8 (10), pp. 1144.en
dc.identifier.issn2073-4409
dc.identifier.urihttps://dora.dmu.ac.uk/handle/2086/18525
dc.descriptionopen access journalen
dc.description.abstractSecond 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 M NE by 50–60%. IC50 for cis- and trans-NED 19 were 2.7 and 8.9 M, respectively. The inhibition by NED 19 stereoisomers of the e ects 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.en
dc.language.isoenen
dc.publisherMDPIen
dc.subjectnorepinephrine;en
dc.subjectcalcium;en
dc.subjecttwo-pore channelsen
dc.subjectsmooth muscle cellsen
dc.subjectNED 19en
dc.subjectNAADPen
dc.subjectsiRNAen
dc.subjectaortaen
dc.titleThe role of two-pore channels in norepinephrine-induced [Ca2+]i rise in rat aortic smooth muscle cells and aorta contraction.en
dc.typeArticleen
dc.identifier.doihttps://doi.org/10.3390/cells8101144
dc.peerreviewedYesen
dc.funderOther external funder (please detail below)en
dc.projectid8-15-00417en
dc.cclicenceCC BYen
dc.date.acceptance2019-09-23
dc.researchinstituteInstitute for Allied Health Sciences Researchen
dc.funder.otherRussian Science Foundationen


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