Adenine attenuates the Ca(2+) contraction-signaling pathway via adenine receptor-mediated signaling in rat vascular smooth muscle cells
Our previous study demonstrated that adenine (6-amino-6H-purine) relaxed contracted rat aorta rings in an endothelial-independent manner. Although adenine receptors (AdeRs) are expressed in diverse tissues, aortic AdeR expression has not been ascertained. Thus, the aims of this study were to clarify...
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| Veröffentlicht in: | Naunyn-Schmiedeberg's archives of pharmacology 2016-09, Vol.389 (9), p.999-1007 |
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| creator | Fukuda, Toshihiko Kuroda, Takahiro Kono, Miki Hyoguchi, Mai Tajiri, Satoshi Tanaka, Mitsuru Mine, Yoshinori Matsui, Toshiro |
| description | Our previous study demonstrated that adenine (6-amino-6H-purine) relaxed contracted rat aorta rings in an endothelial-independent manner. Although adenine receptors (AdeRs) are expressed in diverse tissues, aortic AdeR expression has not been ascertained. Thus, the aims of this study were to clarify the expression of AdeR in rat vascular smooth muscle cells (VSMCs) and to investigate the adenine-induced vasorelaxation mechanism(s). VSMCs were isolated from 8-week-old male Wistar-Kyoto rats and used in this study. Phosphorylation of myosin light chain (p-MLC) was measured by western blot. AdeR mRNA was detected by RT-PCR. Intracellular Ca(2+) concentration ([Ca(2+)]i) was measured by using Fura-2/AM. Vasorelaxant adenine (10-100 μM) significantly reduced p-MLC by angiotensin II (Ang II, 10 μM) in VSMCs (P |
| doi_str_mv | 10.1007/s00210-016-1264-0 |
| format | Article |
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Although adenine receptors (AdeRs) are expressed in diverse tissues, aortic AdeR expression has not been ascertained. Thus, the aims of this study were to clarify the expression of AdeR in rat vascular smooth muscle cells (VSMCs) and to investigate the adenine-induced vasorelaxation mechanism(s). VSMCs were isolated from 8-week-old male Wistar-Kyoto rats and used in this study. Phosphorylation of myosin light chain (p-MLC) was measured by western blot. AdeR mRNA was detected by RT-PCR. Intracellular Ca(2+) concentration ([Ca(2+)]i) was measured by using Fura-2/AM. Vasorelaxant adenine (10-100 μM) significantly reduced p-MLC by angiotensin II (Ang II, 10 μM) in VSMCs (P < 0.05). We confirmed the expression of aortic AdeR mRNA and the activation of PKA in VSMCs through stimulation of AdeR by adenine by ELISA. Intracellular Ca(2+) concentration ([Ca(2+)]i) measurement demonstrated that adenine inhibits Ang II- and m-3M3FBS (PLC agonist)-induced [Ca(2+)]i elevation. In AdeR-knockdown VSMCs, PKA activation and p-MLC reduction by adenine were completely abolished. These results firstly demonstrated that vasorelaxant adenine can suppress Ca(2+) contraction signaling pathways via aortic AdeR/PKA activation in VSMCs.</description><identifier>EISSN: 1432-1912</identifier><identifier>DOI: 10.1007/s00210-016-1264-0</identifier><identifier>PMID: 27318925</identifier><language>eng</language><publisher>Germany</publisher><subject>Adenine - pharmacology ; Angiotensin II - pharmacology ; Animals ; Aorta - drug effects ; Aorta - metabolism ; Cells, Cultured ; Cyclic AMP-Dependent Protein Kinases - metabolism ; Dose-Response Relationship, Drug ; Enzyme Activation ; Excitation Contraction Coupling - drug effects ; Male ; Muscle, Smooth, Vascular - drug effects ; Muscle, Smooth, Vascular - metabolism ; Myocytes, Smooth Muscle - drug effects ; Myocytes, Smooth Muscle - metabolism ; Myosin Light Chains - metabolism ; Phosphorylation ; Purinergic Agonists - pharmacology ; Rats, Inbred WKY ; Receptors, Purinergic - drug effects ; Receptors, Purinergic - genetics ; Receptors, Purinergic - metabolism ; RNA Interference ; Transfection ; Vasodilation - drug effects ; Vasodilator Agents - pharmacology</subject><ispartof>Naunyn-Schmiedeberg's archives of pharmacology, 2016-09, Vol.389 (9), p.999-1007</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27318925$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fukuda, Toshihiko</creatorcontrib><creatorcontrib>Kuroda, Takahiro</creatorcontrib><creatorcontrib>Kono, Miki</creatorcontrib><creatorcontrib>Hyoguchi, Mai</creatorcontrib><creatorcontrib>Tajiri, Satoshi</creatorcontrib><creatorcontrib>Tanaka, Mitsuru</creatorcontrib><creatorcontrib>Mine, Yoshinori</creatorcontrib><creatorcontrib>Matsui, Toshiro</creatorcontrib><title>Adenine attenuates the Ca(2+) contraction-signaling pathway via adenine receptor-mediated signaling in rat vascular smooth muscle cells</title><title>Naunyn-Schmiedeberg's archives of pharmacology</title><addtitle>Naunyn Schmiedebergs Arch Pharmacol</addtitle><description>Our previous study demonstrated that adenine (6-amino-6H-purine) relaxed contracted rat aorta rings in an endothelial-independent manner. Although adenine receptors (AdeRs) are expressed in diverse tissues, aortic AdeR expression has not been ascertained. Thus, the aims of this study were to clarify the expression of AdeR in rat vascular smooth muscle cells (VSMCs) and to investigate the adenine-induced vasorelaxation mechanism(s). VSMCs were isolated from 8-week-old male Wistar-Kyoto rats and used in this study. Phosphorylation of myosin light chain (p-MLC) was measured by western blot. AdeR mRNA was detected by RT-PCR. Intracellular Ca(2+) concentration ([Ca(2+)]i) was measured by using Fura-2/AM. Vasorelaxant adenine (10-100 μM) significantly reduced p-MLC by angiotensin II (Ang II, 10 μM) in VSMCs (P < 0.05). We confirmed the expression of aortic AdeR mRNA and the activation of PKA in VSMCs through stimulation of AdeR by adenine by ELISA. Intracellular Ca(2+) concentration ([Ca(2+)]i) measurement demonstrated that adenine inhibits Ang II- and m-3M3FBS (PLC agonist)-induced [Ca(2+)]i elevation. In AdeR-knockdown VSMCs, PKA activation and p-MLC reduction by adenine were completely abolished. These results firstly demonstrated that vasorelaxant adenine can suppress Ca(2+) contraction signaling pathways via aortic AdeR/PKA activation in VSMCs.</description><subject>Adenine - pharmacology</subject><subject>Angiotensin II - pharmacology</subject><subject>Animals</subject><subject>Aorta - drug effects</subject><subject>Aorta - metabolism</subject><subject>Cells, Cultured</subject><subject>Cyclic AMP-Dependent Protein Kinases - metabolism</subject><subject>Dose-Response Relationship, Drug</subject><subject>Enzyme Activation</subject><subject>Excitation Contraction Coupling - drug effects</subject><subject>Male</subject><subject>Muscle, Smooth, Vascular - drug effects</subject><subject>Muscle, Smooth, Vascular - metabolism</subject><subject>Myocytes, Smooth Muscle - drug effects</subject><subject>Myocytes, Smooth Muscle - metabolism</subject><subject>Myosin Light Chains - metabolism</subject><subject>Phosphorylation</subject><subject>Purinergic Agonists - pharmacology</subject><subject>Rats, Inbred WKY</subject><subject>Receptors, Purinergic - drug effects</subject><subject>Receptors, Purinergic - genetics</subject><subject>Receptors, Purinergic - metabolism</subject><subject>RNA Interference</subject><subject>Transfection</subject><subject>Vasodilation - drug effects</subject><subject>Vasodilator Agents - pharmacology</subject><issn>1432-1912</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkEtOwzAYhC0kREvhAGyQl0XI4GecLKuqPKRKbGAd_XHc1ihxgu0U9QRcmyCKWM3mm9HMIHTF6B2jVN9HSjmjhLKMMJ5JQk_QlEnBCSsYn6DzGN8ppRlT6gxNuBYsL7iaoq9Fbb3zFkNK1g-QbMRpZ_ES5vz2BpvOpwAmuc6T6LYeGue3uIe0-4QD3jvAcPQHa2yfukBaW7sxpsb_vPM4QMJ7iGZoIODYdl3a4XaIprHY2KaJF-h0A020l0edobeH1evyiaxfHp-XizXpx1WJjKU3RV1IMNLkRuisMroCynSRK2mAsVpKmvOi0ForQSHL6kqoWmmRS6OFFjM0_83tQ_cx2JjK1sWfBuBtN8SS5YwqlUmlRvT6iA7VOKrsg2shHMq_88Q33h1wgw</recordid><startdate>201609</startdate><enddate>201609</enddate><creator>Fukuda, Toshihiko</creator><creator>Kuroda, Takahiro</creator><creator>Kono, Miki</creator><creator>Hyoguchi, Mai</creator><creator>Tajiri, Satoshi</creator><creator>Tanaka, Mitsuru</creator><creator>Mine, Yoshinori</creator><creator>Matsui, Toshiro</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>201609</creationdate><title>Adenine attenuates the Ca(2+) contraction-signaling pathway via adenine receptor-mediated signaling in rat vascular smooth muscle cells</title><author>Fukuda, Toshihiko ; Kuroda, Takahiro ; Kono, Miki ; Hyoguchi, Mai ; Tajiri, Satoshi ; Tanaka, Mitsuru ; Mine, Yoshinori ; Matsui, Toshiro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p126t-892f9d94ac4c8c376bc7ba0179854ca11d4408299777530a66db35d57384c7373</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adenine - pharmacology</topic><topic>Angiotensin II - pharmacology</topic><topic>Animals</topic><topic>Aorta - drug effects</topic><topic>Aorta - metabolism</topic><topic>Cells, Cultured</topic><topic>Cyclic AMP-Dependent Protein Kinases - metabolism</topic><topic>Dose-Response Relationship, Drug</topic><topic>Enzyme Activation</topic><topic>Excitation Contraction Coupling - drug effects</topic><topic>Male</topic><topic>Muscle, Smooth, Vascular - drug effects</topic><topic>Muscle, Smooth, Vascular - metabolism</topic><topic>Myocytes, Smooth Muscle - drug effects</topic><topic>Myocytes, Smooth Muscle - metabolism</topic><topic>Myosin Light Chains - metabolism</topic><topic>Phosphorylation</topic><topic>Purinergic Agonists - pharmacology</topic><topic>Rats, Inbred WKY</topic><topic>Receptors, Purinergic - drug effects</topic><topic>Receptors, Purinergic - genetics</topic><topic>Receptors, Purinergic - metabolism</topic><topic>RNA Interference</topic><topic>Transfection</topic><topic>Vasodilation - drug effects</topic><topic>Vasodilator Agents - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fukuda, Toshihiko</creatorcontrib><creatorcontrib>Kuroda, Takahiro</creatorcontrib><creatorcontrib>Kono, Miki</creatorcontrib><creatorcontrib>Hyoguchi, Mai</creatorcontrib><creatorcontrib>Tajiri, Satoshi</creatorcontrib><creatorcontrib>Tanaka, Mitsuru</creatorcontrib><creatorcontrib>Mine, Yoshinori</creatorcontrib><creatorcontrib>Matsui, Toshiro</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Naunyn-Schmiedeberg's archives of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fukuda, Toshihiko</au><au>Kuroda, Takahiro</au><au>Kono, Miki</au><au>Hyoguchi, Mai</au><au>Tajiri, Satoshi</au><au>Tanaka, Mitsuru</au><au>Mine, Yoshinori</au><au>Matsui, Toshiro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Adenine attenuates the Ca(2+) contraction-signaling pathway via adenine receptor-mediated signaling in rat vascular smooth muscle cells</atitle><jtitle>Naunyn-Schmiedeberg's archives of pharmacology</jtitle><addtitle>Naunyn Schmiedebergs Arch Pharmacol</addtitle><date>2016-09</date><risdate>2016</risdate><volume>389</volume><issue>9</issue><spage>999</spage><epage>1007</epage><pages>999-1007</pages><eissn>1432-1912</eissn><abstract>Our previous study demonstrated that adenine (6-amino-6H-purine) relaxed contracted rat aorta rings in an endothelial-independent manner. Although adenine receptors (AdeRs) are expressed in diverse tissues, aortic AdeR expression has not been ascertained. Thus, the aims of this study were to clarify the expression of AdeR in rat vascular smooth muscle cells (VSMCs) and to investigate the adenine-induced vasorelaxation mechanism(s). VSMCs were isolated from 8-week-old male Wistar-Kyoto rats and used in this study. Phosphorylation of myosin light chain (p-MLC) was measured by western blot. AdeR mRNA was detected by RT-PCR. Intracellular Ca(2+) concentration ([Ca(2+)]i) was measured by using Fura-2/AM. Vasorelaxant adenine (10-100 μM) significantly reduced p-MLC by angiotensin II (Ang II, 10 μM) in VSMCs (P < 0.05). We confirmed the expression of aortic AdeR mRNA and the activation of PKA in VSMCs through stimulation of AdeR by adenine by ELISA. Intracellular Ca(2+) concentration ([Ca(2+)]i) measurement demonstrated that adenine inhibits Ang II- and m-3M3FBS (PLC agonist)-induced [Ca(2+)]i elevation. In AdeR-knockdown VSMCs, PKA activation and p-MLC reduction by adenine were completely abolished. These results firstly demonstrated that vasorelaxant adenine can suppress Ca(2+) contraction signaling pathways via aortic AdeR/PKA activation in VSMCs.</abstract><cop>Germany</cop><pmid>27318925</pmid><doi>10.1007/s00210-016-1264-0</doi><tpages>9</tpages></addata></record> |
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| subjects | Adenine - pharmacology Angiotensin II - pharmacology Animals Aorta - drug effects Aorta - metabolism Cells, Cultured Cyclic AMP-Dependent Protein Kinases - metabolism Dose-Response Relationship, Drug Enzyme Activation Excitation Contraction Coupling - drug effects Male Muscle, Smooth, Vascular - drug effects Muscle, Smooth, Vascular - metabolism Myocytes, Smooth Muscle - drug effects Myocytes, Smooth Muscle - metabolism Myosin Light Chains - metabolism Phosphorylation Purinergic Agonists - pharmacology Rats, Inbred WKY Receptors, Purinergic - drug effects Receptors, Purinergic - genetics Receptors, Purinergic - metabolism RNA Interference Transfection Vasodilation - drug effects Vasodilator Agents - pharmacology |
| title | Adenine attenuates the Ca(2+) contraction-signaling pathway via adenine receptor-mediated signaling in rat vascular smooth muscle cells |
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