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

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 furth...

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Autores principales: Greenberg, Harry Z. E., Carlton Carew, Simonette R. E., Zargaran, Alexander K., Jahan, Kazi S., Birnbaumer, Lutz, Albert, Anthony P.
Formato: Artículo
Lenguaje:Inglés
Publicado: Taylor & Francis 2020
Materias:
TRPC1
TRPV4
OXIDO NITRICO
CALCIO
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/9807
Aporte de:
Repositorio Institucional de la Universidad Católica Argentina (UCA) de Universidad Católica Argentina
id I33-R139123456789-9807
record_format dspace
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
topic TRPC1
TRPV4
OXIDO NITRICO
CALCIO
spellingShingle TRPC1
TRPV4
OXIDO NITRICO
CALCIO
Greenberg, Harry Z. E.
Carlton Carew, Simonette R. E.
Zargaran, Alexander K.
Jahan, Kazi S.
Birnbaumer, Lutz
Albert, Anthony P.
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
topic_facet TRPC1
TRPV4
OXIDO NITRICO
CALCIO
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.
format Artículo
author Greenberg, Harry Z. E.
Carlton Carew, Simonette R. E.
Zargaran, Alexander K.
Jahan, Kazi S.
Birnbaumer, Lutz
Albert, Anthony P.
author_facet Greenberg, Harry Z. E.
Carlton Carew, Simonette R. E.
Zargaran, Alexander K.
Jahan, Kazi S.
Birnbaumer, Lutz
Albert, Anthony P.
author_sort Greenberg, Harry Z. E.
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
title_short 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_sort 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
publisher Taylor & Francis
publishDate 2020
url https://repositorio.uca.edu.ar/handle/123456789/9807
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