McCall D, Fried T A
Department of Medicine, University of Texas Health Science Center, San Antonio 78284.
J Mol Cell Cardiol. 1990 Feb;22(2):201-12. doi: 10.1016/0022-2828(90)91116-o.
The present study was carried out to evaluate the effects of biologically active atriopeptin II (APII) in synchronously contracting monolayer cultures of rat ventricular myocytes. The effects of 10 nM APII on Ca influx, contractile behavior and cyclic nucleotide content of the cells were measured. Applied acutely APII had no effect on Ca influx. There was however a time-dependent effect such that after 30 min Ca influx (pmol/cm2/s) had declined from a control (mean +/- S.E.M.) of 1.53 +/- 0.16 to 1.02 +/- 0.07 (P less than 0.001; n = 6). There was parallel decline in both the magnitude and velocity of cell edge motion which was maximal in 30 min at which time cell edge motion measured 65.3 +/- 4.4% of control. Treatment with APII for 30 min decreased cAMP (pmol/mg protein) from 5.35 +/- 0.17 to 2.86 +/- 0.24 (P less than 0.001; n = 5). At the same time cGMP (pmol/mg protein) increased from 0.86 +/- 0.21 to 2.14 +/- 0.33 (P less than 0.001; n = 5). Further studies elucidated the fact that the decline in Ca influx and contractile behavior was dependent on the decrease in cAMP rather than the increase in cGMP. Pre-treatment of the cells with 5 ng/ml of pertussis toxin to ADP-ribosylate the Gi protein abolished the effects of APII on cAMP, Ca influx and contractile behavior. The results indicate that in myocardial cells, as in other cells, APII stimulates guanylate cyclase and inhibits adenylate cyclase. The resultant fall in cAMP decreases Ca influx and negatively influences the contractile behavior of the cells.
本研究旨在评估生物活性心房肽II（APII）对大鼠心室肌细胞同步收缩单层培养物的影响。测量了10 nM APII对细胞钙内流、收缩行为和环核苷酸含量的影响。急性应用APII对钙内流无影响。然而，存在时间依赖性效应，即30分钟后钙内流（pmol/cm²/s）从对照（平均值±标准误）的1.53±0.16降至1.02±0.07（P<0.001；n = 6）。细胞边缘运动的幅度和速度也出现平行下降，在30分钟时达到最大，此时细胞边缘运动为对照的65.3±4.4%。用APII处理30分钟可使环磷酸腺苷（cAMP，pmol/mg蛋白质）从5.35±0.17降至2.86±0.24（P<0.001；n = 5）。同时，环磷酸鸟苷（cGMP，pmol/mg蛋白质）从0.86±0.21增加至2.14±0.33（P<0.001；n = 5）。进一步研究表明，钙内流和收缩行为的下降依赖于cAMP的减少而非cGMP的增加。用5 ng/ml百日咳毒素预处理细胞使Gi蛋白进行ADP核糖基化，消除了APII对cAMP、钙内流和收缩行为的影响。结果表明，在心肌细胞中，与其他细胞一样，APII刺激鸟苷酸环化酶并抑制腺苷酸环化酶。由此导致的cAMP下降减少了钙内流，并对细胞的收缩行为产生负面影响。
