Analysis of potential molecular targets in the beta-adrenergic receptor signal pathway for new drug therapy of catecholamine-induced arrhythmias

2014 Fiscal Year Final Research Report

• Project/Area Number: 24790219
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General physiology
• Research Institution: Yokohama City University
• Principal Investigator: SUITA KENJI 横浜市立大学, 医学(系)研究科(研究院), 特任助手 (90569542)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 不整脈 / 分子標的薬 / ベータアドレナリン受容体 / アデニル酸シクラーゼ / cAMP / Epac

Outline of Final Research Achievements

Adenylyl cyclase (AC) and Epac, a target molecule of cAMP, play critical roles in beta-adrenergic receptor (β-AR) signaling in heart. The usefulness of β-AR antagonist (β-blocker) for the treatment of catecholamine-induced AF and ventricular arrhythmias is established. However, even low dosage of β-blockers exert negative-inotropic effect and may cause a deterioration of heart function. We found that vidarabine, an anti-herpesvirus agent, is a selective inhibitor of cardiac AC subtype. Here, we evaluated the anti-arrhythmic effect of vidarabine using our AF model, in which the duration of AF is strikingly elongated by noradrenaline, and a previously established model of ventricular arrhythmias.
Results indicate that vidarabine prevents catecholamine-induced AF and ventricular arrhythmias without deterioration of heart function. On the other hand, the AF duration of Epac1 gene-knockout mice was shorter than that of wild-type mice, suggesting that Epac1 plays an important role in AF.

Free Research Field

分子細胞生物学