Functional relevance of the changes in cyclic AMP accumulation.

在离体大鼠心肌细胞和乳头状muscle.Methods：异丙肾上腺素（ISP），磷酸二酯酶（PDE）和ISP在PDE抑制剂的存在下对收缩力的影响的cAMP代谢的变化的功能相关性进行了检查。在离体大鼠右乳头肌中测量收缩力（37 ° C，1Hz）。采用Powell和Twist法分离大鼠心肌细胞，放射免疫法测定cAMP含量。结果如下：次最大浓度的ISP和IBMX（一种非选择性PDE抑制剂）诱导的cAMP蓄积程度分别为2.4和4.8倍。但IBMX的正性肌力作用（PIE）不如ISP。IBMX本身引起cAMP的积累和PIE，并增强ISP诱导的cAMP积累和PIE。PDE III型选择性抑制剂（米力农）引起cAMP积累和PIE本身。而米力农对ISP诱导的cAMP积累和PIE几乎没有影响。PDE IV型选择性抑制剂Ro 20-1724本身不引起cAMP蓄积和PIE，但它比IBMX更有效地增强ISP诱导的cAMP蓄积和PIE。因此，细胞内cAMP浓度的增加不一定反映为收缩力的增强。本研究结果表明，cAMP和PDE同工酶在不同的细胞内室共享不同的生理相关性，在调节心肌收缩力。

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.