Cui Xun, Wen Jin Fu, Jin Jing Yu, Xu Wen Xie, Kim Sung Zoo, Kim Suhn Hee, Lee Ho Sub, Cho Kyung Woo
Department of Physiology, Institute for Medical Sciences, Jeonbug National University Medical School, Jeonju 561-180, Korea.
Am J Physiol Regul Integr Comp Physiol. 2002 May;282(5):R1477-89. doi: 10.1152/ajpregu.00316.2001.
Regulation of atrial release of atrial natriuretic peptide (ANP) is coupled to changes in atrial dynamics. However, the mechanism by which mechanical stretch controls myocytic ANP release must be defined. The purpose of this study was to define the mechanism by which cAMP controls myocytic ANP release in perfused, beating rabbit atria. The cAMP-elevating agents forskolin and 3-isobutyl-1-methylxanthine (IBMX) inhibited myocytic ANP release. The activation of adenylyl cyclase with forskolin inhibited ANP release, which was a function of an increase in cAMP production. Inhibitors for L-type Ca(2+) channels and protein kinase A (PKA) attenuated a minor portion of the forskolin-induced inhibition of ANP release. Gö-6976 and KN-62, which are specific inhibitors for protein kinase C-alpha and Ca(2+)/calmodulin kinase, respectively, failed to modulate forskolin-induced inhibition of ANP release. The nonspecific protein kinase inhibitor staurosporine blocked forskolin-induced inhibition of ANP release in a dose-dependent manner. Staurosporine but not nifedipine shifted the relationship between cAMP and ANP release. Inhibitors for L-type Ca(2+) channels and PKA and staurosporine blocked forskolin-induced accentuation of atrial dynamics. These results suggest that cAMP inhibits atrial myocytic release of ANP via protein kinase-dependent and L-type Ca(2+)-channel-dependent and -independent signaling pathways.
心房利钠肽（ANP）的心房释放调节与心房动力学变化相关联。然而，机械牵张控制心肌细胞ANP释放的机制仍有待明确。本研究的目的是确定环磷酸腺苷（cAMP）在灌注跳动的兔心房中控制心肌细胞ANP释放的机制。升高cAMP的药物福斯可林和3 - 异丁基 - 1 - 甲基黄嘌呤（IBMX）抑制心肌细胞ANP释放。用福斯可林激活腺苷酸环化酶可抑制ANP释放，这是cAMP生成增加的结果。L型钙通道和蛋白激酶A（PKA）的抑制剂减弱了福斯可林诱导的ANP释放抑制的一小部分。分别作为蛋白激酶C - α和钙/钙调蛋白激酶特异性抑制剂的Gö - 6976和KN - 62未能调节福斯可林诱导的ANP释放抑制。非特异性蛋白激酶抑制剂星形孢菌素以剂量依赖性方式阻断福斯可林诱导的ANP释放抑制。星形孢菌素而非硝苯地平改变了cAMP与ANP释放之间的关系。L型钙通道和PKA的抑制剂以及星形孢菌素阻断了福斯可林诱导的心房动力学增强。这些结果表明，cAMP通过蛋白激酶依赖性以及L型钙通道依赖性和非依赖性信号通路抑制心房肌细胞释放ANP。
