دورية أكاديمية
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.
العنوان: | 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. |
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المؤلفون: | Greenberg HZE; Vascular Biology Research Centre, Molecular & Clinical Sciences Research Institute, St. George's, University of London, London, UK., Carlton-Carew SRE; Vascular Biology Research Centre, Molecular & Clinical Sciences Research Institute, St. George's, University of London, London, UK., Zargaran AK; Vascular Biology Research Centre, Molecular & Clinical Sciences Research Institute, St. George's, University of London, London, UK., Jahan KS; Vascular Biology Research Centre, Molecular & Clinical Sciences Research Institute, St. George's, University of London, London, UK., Birnbaumer L; Laboratory of Neurobiology, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.; Institute of Biomedical Research (BIOMED), Catholic University of Argentina, Buenos Aires, Argentina., Albert AP; Vascular Biology Research Centre, Molecular & Clinical Sciences Research Institute, St. George's, University of London, London, UK. |
المصدر: | Channels (Austin, Tex.) [Channels (Austin)] 2019 Dec; Vol. 13 (1), pp. 410-423. Date of Electronic Publication: 2019 Oct 11. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Taylor & Francis Country of Publication: United States NLM ID: 101321614 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1933-6969 (Electronic) Linking ISSN: 19336950 NLM ISO Abbreviation: Channels (Austin) Subsets: MEDLINE |
أسماء مطبوعة: | Publication: 2015- : Philadelphia, PA : Taylor & Francis Original Publication: Austin, Tex. : Landes Bioscience, c2007- |
مواضيع طبية MeSH: | Mesenteric Arteries/*metabolism , Nitric Oxide/*metabolism , Receptors, Calcium-Sensing/*metabolism , TRPC Cation Channels/*metabolism , TRPV Cation Channels/*metabolism, Animals ; Calcium/metabolism ; Calcium Signaling ; Dimerization ; Endothelial Cells/metabolism ; Female ; Male ; Mice ; Mice, Knockout ; Rabbits ; Receptors, Calcium-Sensing/genetics ; TRPC Cation Channels/chemistry ; TRPC Cation Channels/genetics ; TRPV Cation Channels/chemistry ; TRPV Cation Channels/genetics ; Vasodilation |
مستخلص: | 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. |
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معلومات مُعتمدة: | BB/M018350/1 United Kingdom BB_ Biotechnology and Biological Sciences Research Council; Z01 ES101684 United States ES NIEHS NIH HHS; FS/17/40/32942 United Kingdom BHF_ British Heart Foundation; FS/13/10/30021 United Kingdom BHF_ British Heart Foundation; Z01 ES101684 United States ImNIH Intramural NIH HHS; BB/J007226/1 United Kingdom BB_ Biotechnology and Biological Sciences Research Council |
فهرسة مساهمة: | Keywords: Calcium-sensing receptors; TRPC1; TRPV4; endothelium; nitric oxide; vascular smooth muscle |
المشرفين على المادة: | 0 (CASR protein, mouse) 0 (Receptors, Calcium-Sensing) 0 (TRPC Cation Channels) 0 (TRPV Cation Channels) 0 (Trpv4 protein, mouse) 0 (transient receptor potential cation channel, subfamily C, member 1) 31C4KY9ESH (Nitric Oxide) SY7Q814VUP (Calcium) |
تواريخ الأحداث: | Date Created: 20191012 Date Completed: 20200713 Latest Revision: 20220129 |
رمز التحديث: | 20240628 |
مُعرف محوري في PubMed: | PMC7426016 |
DOI: | 10.1080/19336950.2019.1673131 |
PMID: | 31603369 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1933-6969 |
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DOI: | 10.1080/19336950.2019.1673131 |