| Urotensin-II Signaling Mechanism in Rat Coronary Artery: Role of STIM1 and Orai1-Dependent Store Operated Calcium Influx in Vasoconstriction. | |
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MedLine Citation:
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PMID: 22223729 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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OBJECTIVE: Human urotensin-II (UII) is considered the most potent endogenous vasoconstrictor discovered to date, although the precise mechanism activated downstream of its receptor UTS2R in blood vessels remains elusive. The aim of this study was to determine the role of the store operated Ca(2+ )entry (SOCE) signaling pathway in UII-induced coronary artery vasoconstriction. METHODS AND RESULTS: We used a combination of isometric tension measurement, Ca(2+) imaging, pharmacology, and molecular approaches to study UII-mediated rat coronary artery vasoconstriction and intracellular Ca(2+) mobilization in coronary smooth muscle cells. We found that UII promoted dose-dependent vasoconstriction and elicited Ca(2+) and Mn(2+) influx, which were sensitive to classical SOCE inhibitors. In addition, knockdown of either STIM1 or Orai1 essentially inhibited UII-mediated SOCE and prevented UII but not high-KCL evoked contraction in transfected coronary artery. Moreover, we found that Ca(2+)-independent phospholipase A(2)β was involved in UII effects and that is colocalized with STIM1 in different submembrane compartments. Importantly, STIM1 but not Orai1 downregulation inhibits significantly independent phospholipase A(2) activation. Furthermore, lysophosphatidylcholine, an independent phospholipase A(2) product, activated Orai1 but not STIM1-dependent contraction and SOCE. CONCLUSIONS: Here, we demonstrated that different critical players of SOCE signaling pathway are required for UII-induced vasoconstriction of rat coronary artery. |
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Authors:
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Alejandro Domínguez-Rodríguez; Ignacio Díaz; María Rodríguez-Moyano; Eva Calderón-Sánchez; Juan Antonio Rosado; Antonio Ordóñez; Tarik Smani |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-5 |
Journal Detail:
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Title: Arteriosclerosis, thrombosis, and vascular biology Volume: - ISSN: 1524-4636 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-6 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9505803 Medline TA: Arterioscler Thromb Vasc Biol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Group of Cardiovascular Physiopathology, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain; Department of Physiology, Universidad de Extremadura, Cáceres, Spain. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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