发明名称 |
COMPOSITIONS AND METHODS FOR REGULATING BLOOD PRESSURE |
摘要 |
Both purinergic signaling through nucleotides such as ATP and noradrenergic signaling through molecules such as norepinephrine regulate vascular tone and blood pressure. Pannexin1 (Panx1), which forms large-pore, ATP-releasing channels, is present in vascular smooth muscle cells in peripheral blood vessels and participates in noradrenergic responses. Using pharmacological approaches and mice conditionally lacking Panx1 in smooth muscle cells, we found that Panx1 contributed to vasoconstriction mediated by the α1 adrenoreceptor (α1AR), whereas vasoconstriction in response to serotonin or endothelin-1 was independent of Panx1. Analysis of the Panx1-deficient mice showed that Panx1 contributed to blood pressure regulation especially during the night cycle when sympathetic nervous activity is highest. Using mimetic peptides and site-directed mutagenesis, we identified a specific amino acid sequence in the Panx1 intracellular loop that is essential for activation by α1AR signaling. Collectively, these data describe a specific link between noradrenergic and purinergic signaling in blood pressure homeostasis. |
申请公布号 |
WO2016130966(A1) |
申请公布日期 |
2016.08.18 |
申请号 |
WO2016US17830 |
申请日期 |
2016.02.12 |
申请人 |
UNIVERSITY OF VIRGINIA PATENT FOUNDATION |
发明人 |
ISAKSON, Brant E.;BILLAUD, Marie;DELALIO, Leon J.;LE, Thu |
分类号 |
A61K38/08;A61K38/16;A61P9/00;A61P9/08 |
主分类号 |
A61K38/08 |
代理机构 |
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代理人 |
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地址 |
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