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dc.contributor.author
Greenberg, Harry Z.E.
dc.contributor.author
Carlton Carew, Simonette R.E.
dc.contributor.author
Zargaran, Alexander K.
dc.contributor.author
Jahan, Kazi S.
dc.contributor.author
Birnbaumer, Lutz
dc.contributor.author
Albert, Anthony P.
dc.date.available
2020-12-18T12:31:54Z
dc.date.issued
2019-01
dc.identifier.citation
Greenberg, Harry Z.E.; Carlton Carew, Simonette R.E.; Zargaran, Alexander K.; Jahan, Kazi S.; Birnbaumer, Lutz; et al.; Heteromeric TRPV4/TRPC1 channels mediate calcium-sensing receptor-induced relaxations and nitric oxide production in mesenteric arteries: comparative study using wild-type and TRPC1−/- mice; Landes Bioscience; Channels; 13; 1; 1-2019; 410-423
dc.identifier.issn
1933-6950
dc.identifier.uri
http://hdl.handle.net/11336/120817
dc.description.abstract
We have previously provided pharmacological evidence that stimulation of calcium-sensing receptors (CaSR) induces endothelium-dependent relaxations of rabbit mesenteric arteries through activation of heteromeric TRPV4/TRPC1 channels and nitric oxide (NO) production. The present study further investigates the role of heteromeric TRPV4/TRPC1 channels in these CaSR-induced vascular responses by comparing responses in mesenteric arteries from wild-type (WT) and TRPC1-/- mice. In WT mice, stimulation of CaSR induced endothelium-dependent relaxations of pre-contracted tone and NO generation in endothelial cells (ECs), which were inhibited by the TRPV4 channel blocker RN1734 and the TRPC1 blocking antibody T1E3. In addition, TRPV4 and TRPC1 proteins were colocalised at, or close to, the plasma membrane of endothelial cells (ECs) from WT mice. In contrast, in TRPC1-/- mice, CaSR-mediated vasorelaxations and NO generation were greatly reduced, unaffected by T1E3, but blocked by RN1734. In addition, the TRPV4 agonist GSK1016790A (GSK) induced endothelium-dependent vasorelaxations which were blocked by RN1734 and T1E3 in WT mice, but only by RN1734 in TRPC1-/- mice. Moreover, GSK activated cation channel activity with a 6pS conductance in WT ECs but with a 52 pS conductance in TRPC1-/- ECs. These results indicate that stimulation of CaSR activates heteromeric TRPV4/TRPC1 channels and NO production in ECs, which are responsible for endothelium-dependent vasorelaxations. This study also suggests that heteromeric TRPV4-TRPC1 channels may form the predominant TRPV4-containing channels in mouse mesenteric artery ECs. Together, our data further implicates CaSR-induced pathways and heteromeric TRPV4/TRPC1 channels in the regulation of vascular tone.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Landes Bioscience
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc/2.5/ar/
dc.subject
CALCIUM-SENSING RECEPTORS
dc.subject
ENDOTHELIUM
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NITRIC OXIDE
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TRPC1
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TRPV4
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VASCULAR SMOOTH MUSCLE
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Biología Celular, Microbiología
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
Heteromeric TRPV4/TRPC1 channels mediate calcium-sensing receptor-induced relaxations and nitric oxide production in mesenteric arteries: comparative study using wild-type and TRPC1−/- mice
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2020-11-25T16:38:19Z
dc.journal.volume
13
dc.journal.number
1
dc.journal.pagination
410-423
dc.journal.pais
Estados Unidos
dc.description.fil
Fil: Greenberg, Harry Z.E.. City University of London; Reino Unido
dc.description.fil
Fil: Carlton Carew, Simonette R.E.. City University of London; Reino Unido
dc.description.fil
Fil: Zargaran, Alexander K.. City University of London; Reino Unido
dc.description.fil
Fil: Jahan, Kazi S.. City University of London; Reino Unido
dc.description.fil
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
dc.description.fil
Fil: Albert, Anthony P.. City University of London; Reino Unido
dc.journal.title
Channels
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1080/19336950.2019.1673131
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