| Project/Area Number |
03670090
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
General pharmacology
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| Research Institution | Yamagata University |
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Principal Investigator |
KATANO Yumi Yamagata Univ,Sch of Med, Associ. Prof., 医学部, 助教授 (70018696)
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| Project Period (FY) |
1991 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1992: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1991: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | cyclic AMP / myocardial contractility / phosphodiesterase / isoproterenol / milrinone / IBMX / Ro 20-1724 / rat myocyte / Cyclic AMP / ラット単離心室筋細胞 / 収縮張力 / β-刺激増強効果 / 細胞内コンパートメント / ホスホジエステラ-ゼ阻害薬 / cyclic AMP / 強心作用 / Milrinone / Yー20487 / Ro20ー1724 / Rolipram |
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| Research Abstract |
Functional relevance of the change in cAMP accumulation was examined in the isolated rat cardiac myocyte and papillary muscle.
Methods: Effects of isoproterenol (ISP), phophodiesterases (PDE) and ISP in the presence of PDE inhibitors on force of contraction were examined in relation to the effects on cAMP metabolism. Force of contraction was measured in the isolated rat right papillary muscle (37ﾟC, 1Hz). Rat heart cell was isolated by method of Powell and Twist and the cAMP content was determined by radioimmunoassay. Results: The extent of cAMP accumulation induced by submaximal concentration of ISP and IBMX (a non-selective PDE inhibitor) was 2.4 and 4.8-fold, respectively. However, IBMX-induced positive inotropic effect (PIE) was less effective than that of ISP. IBMX elicited cAMP accumulation and PIE by itself, and enhanced the ISP-induced cAMP accumulation and PIE. A PDE type-III selective inhibitor (milrinone) elicited cAMP accumulation and PIE by itself. Whereas milrinone scarcely affected the ISP-induced cAMP accumulation and PIE. A PDE type-IV selective inhibitor (Ro 20-1724) did not elicit the cAMP accumulation and PIE by itself, but it potentiated the cAMP accumulation and PIE induced by ISP more effectively than IBMX. Thus increased intracellular cAMP concentration is not necessarily reflected to the augmentation of contractile force. The present results suggest that cAMP and isoenzymes of PDE in the different intracellular compartments share differential physiologic relevance in regulation of myocardial contractility.
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