Effects of EP4 receptor agonist on the left ventricular diastolic function, and analysis of its mechanism
Project/Area Number |
16K08559
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
General pharmacology
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Research Institution | Toho University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
中村 裕二 東邦大学, 医学部, 助教 (10614894)
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Keywords | 拡張不全型心不全 / 収縮不全型心不全 / ONO-AE1-329 / caldaret / EP4受容体 / 細胞内Ca2+ / SERCA / Caldaret / HFpEF / HFrEF / 慢性房室ブロック犬 / EP4受容体刺激 / 左室圧容積関係 / 拡張性心不全 / 左室等容性弛緩能 / 充満期拡張能 |
Outline of Final Research Achievements |
EP4 receptor stimulation by ONO-AE1-329 showed the positive inotropic and lusitopic effects in addition to the increase of left ventricular end-diastolic volume and the decrease of end-systolic volume in normal dogs. The positive inotropic action of ONO-AE1-329 was also confirmed in the chronic heart failure model induced by chronic atrioventricular block, but the lusitropic action were various and bidirectional. Furthermore, intracellular Ca2+ modulation by caldaret was assessed in normal dogs, showing that it can exert various kinds of electropharmacologic actions as well as the positive inotropic and lusitropic effects. Elucidation of the further mechanism at the cellular level may be necessary for analyzing how the change in the intracellular Ca2+ dynamics may affect each of ionic channels in the heart.
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Academic Significance and Societal Importance of the Research Achievements |
拡張不全型心不全は全心不全患者の半数以上を占め、予後不良である。拡張不全型心不全に対して、収縮不全型心不全の治療において予後改善が認められた薬物(レニン・アンジオテンシン系抑制薬およびβ遮断薬など)の有用性が評価されたが、同様の効果は認められず左室拡張機能を修復できる薬物の開発が強く求められていた。本研究では正常犬および拡張不全型心不全モデル犬を用いて新規作用点(EP4受容体刺激および細胞内Ca2+動態修飾)を有する化合物の心血管作用を評価した。得られた知見は、拡張不全型心不全に対しする薬物治療の突破口になることが期待できる。
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Report
(4 results)
Research Products
(34 results)
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[Journal Article] Sunitinib does not acutely alter left ventricular systolic function, but induces diastolic dysfunction2018
Author(s)
Wada T, Ando K, Naito AT, Nakamura Y, Goto A, Chiba K, Lubna NJ, Cao X, Hagiwara-Nagasawa M, Izumi-Nakaseko H, Nakazato Y, Sugiyama A
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Journal Title
Cancer Chemother Pharmacol.
Volume: -
Issue: 1
Pages: 65-75
DOI
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Peer Reviewed / Int'l Joint Research
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[Journal Article] In vivo analysis of the anti-atrial fibrillatory, proarrhythmic and cardiodepressive profiles of dronedarone as a guide for safety pharmacological evaluation of antiarrhythmic drugs2018
Author(s)
Motokawa Y, Nakamura Y, Hagiwara-Nagasawa M, Goto A, Chiba K, Lubna NJ, Izumi-Nakaseko H, Ando K, Naito AT, Yamazaki H, Sugiyama A
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Journal Title
Cardiovascular toxicology
Volume: 印刷中
Issue: 3
Pages: 242-251
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Changes of electrocardiogram and hemodynamics in response to dipyridamole: In vivo comparative analyses using anesthetized beagle dogs and microminipigs2018
Author(s)
Ando K, Takahara A, Nakamura Y, Wada T, Chiba K, Goto A, Lubna NJ, Hagiwara-Nagasawa M, Izumi-Nakaseko H, Hoshiai K, Akie Y, Naito AT, Sugiyama A
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Journal Title
Journal of pharmacological sciences
Volume: 136
Issue: 2
Pages: 86-92
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Comparison of electropharmacological effects between terfenadine and its active derivative fexofenadine using a cross-over study in halothane-anesthetized dogs to analyze variability of pharmacodynamic and pharmacokinetic profiles of terfenadine and torsadogenic risk of fexofenadine2018
Author(s)
Ando K, Nakamura Y, Hagiwara-Nagasawa M, Harada H, Miyamoto H, Inamura N, Takagi K, Goto A, Chiba K, Lubnaa NJ, Izumi-Nakaseko H, Naito AT, Sugiyama A
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Journal Title
The Journal of Toxicological Sciences
Volume: 43
Issue: 3
Pages: 183-192
DOI
NAID
ISSN
0388-1350, 1880-3989
Related Report
Peer Reviewed / Open Access
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[Journal Article] Effects of Red Wine Vinegar Beverage on the Colonic Tissue of Rodents: Biochemical, Functional and Pharmacological Analyses2018
Author(s)
Enkhsaikhan A, Takahara A, Nakamura Y, Goto A, Chiba K, Lubna NJ, Hagiwara-Nagasawa M, Izumi-Nakaseko H, Ando K, Naito AT, Sugiyama A
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Journal Title
Biological and Pharmaceutical Bulletin
Volume: 41
Issue: 2
Pages: 281-284
DOI
NAID
ISSN
0918-6158, 1347-5215
Related Report
Peer Reviewed / Open Access
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[Journal Article] Development of an Educational Equipment “Dock-kun" to Help School Children Master High-quality Cardiac Massage2017
Author(s)
Nakamura Y, Miyamoto T, Yamada M†, Goto A, Hagiwara-Nagasawa M, Izumi-Nakaseko H, Ando K, Honda M, Naito AT, Yoshihara K, Lurie KG, Sugiyama A
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Journal Title
Toho Journal of Medicine
Volume: 3
Issue: 4
Pages: 146-151
DOI
NAID
ISSN
2189-1990
URL
Year and Date
2017-12-01
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Assessment of Pharmacological Effects of Mongolian Medicinal Plant Adonis mongolica in Guinea Pigs in vivo and in vitro2017
Author(s)
Izumi-Nakaseko H, Li W, Cao X, Nakamura Y, Ando K, Tanaka K, Enkhsaikhan A, Gotov C, Purevjav B, Chultemsuren Y, Nyambayar K, Dorjsuren N, Hagiwara-Nagasawa M, Naito AT, Koike K, Sugiyama A
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Journal Title
Toho Journal of Medicine
Volume: 3
Issue: 4
Pages: 131-141
DOI
NAID
ISSN
2189-1990
URL
Year and Date
2017-12-01
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Efficacy of Precordial Percussion Pacing Assessed in a Cardiac Standstill <i>Microminipig</i> Model2017
Author(s)
Wada T, Ohara H, Nakamura Y, Cao X, Izumi-Nakaseko H, Ando K, Honda M, Yoshihara K, Nakazato Y, Lurie KG, Sugiyama A
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Journal Title
Circulation Journal
Volume: 81
Issue: 8
Pages: 1137-1143
DOI
NAID
ISSN
1346-9843, 1347-4820
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Pharmacological characterization of <i>microminipig</i> as a model to assess the drug-induced cardiovascular responses for non-clinical toxicity and/or safety pharmacology studies2017
Author(s)
Yokoyama H, Nakamura Y, Saito H, Nagayama Y, Hoshiai K, Wada T, Izumi-Nakaseko H, Ando K, Akie Y, Sugiyama A
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Journal Title
The Journal of Toxicological Sciences
Volume: 42
Issue: 1
Pages: 93-101
DOI
NAID
ISSN
0388-1350, 1880-3989
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] M201-Aは高い有効性と安全性を有する心房細動治療薬候補化合物である2017
Author(s)
萩原美帆子, 中村裕二, 岩田邦男, 後藤愛, 千葉浩輝, Nur Jaharat Lubna, 中瀬古(泉)寛子, 安東賢太郎, 内藤篤彦, 金子昇, 杉山篤
Organizer
第三回 J-ISCP学術集会
Related Report
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