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Functional relevance of the changes in cyclic AMP accumulation.

环 AMP 积累变化的功能相关性。

基本信息

批准号：
03670090
负责人：
KATANO Yumi
金额：
$ 1.28万
依托单位：
Yamagata University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

项目摘要

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.

在离体大鼠心肌细胞和乳头肌中检测cAMP积累变化的功能相关性。方法：观察异丙肾上腺素（ISP）、磷酸二酯酶（PDE）和磷酸二酯酶在PDE抑制剂存在下对收缩力的影响以及对cAMP代谢的影响。测量离体大鼠右乳头肌（37‰，1Hz）的收缩力。采用Powell法和Twist法分离大鼠心脏细胞，用放射免疫法测定其cAMP含量。结果：ISP和IBMX（一种非选择性PDE抑制剂）亚最大浓度诱导的cAMP蓄积程度分别为2.4倍和4.8倍。然而，ibmx诱导的正性肌力效应（PIE）不如ISP有效。IBMX自身诱导cAMP积累和PIE，并增强isp诱导的cAMP积累和PIE。PDE iii型选择性抑制剂（米立酮）可诱导cAMP积累和PIE。而米力酮几乎不影响isp诱导的cAMP积累和PIE。PDE iv型选择性抑制剂（ro20 -1724）本身不引起cAMP积累和PIE，但比IBMX更有效地增强了ISP诱导的cAMP积累和PIE。因此，细胞内cAMP浓度的增加并不一定反映为收缩力的增强。本研究结果表明，cAMP和PDE同工酶在调节心肌收缩力方面具有不同的生理相关性。