Haneda M, Kikkawa R, Maeda S, Togawa M, Koya D, Horide N, Kajiwara N, Shigeta Y
Third Department of Medicine, Shiga University of Medical Science, Japan.
Kidney Int. 1991 Aug;40(2):188-94. doi: 10.1038/ki.1991.199.
To evaluate an interaction between vasoconstrictive (Ang II) and vasodilating (ANP) peptides, we examined the effect of Ang II on ANP-induced accumulation of cGMP in cultured glomerular mesangial cells. ANP rapidly increased intracellular cGMP levels, with a peak stimulation at one minute in the absence of IBMX and at ten minutes in the presence of IBMX. The ANP-induced cGMP accumulation was significantly inhibited when the cells were treated with Ang II simultaneously with ANP for one minute in the absence of IBMX. This inhibitory effect of Ang II was completely abolished by IBMX and significantly reduced in calcium-free media or by W7, but not affected by H7. Similar inhibitory effect was observed when cells were treated with A23187 but not with TPA for one minute. In the presence of IBMX, Ang II inhibited ANP-induced cGMP accumulation when cells were treated with Ang II for 15 minutes prior to the stimulation by ANP. This inhibition by Ang II was blocked by H7. ANP-induced increase in particulate guanylate cyclase activity was significantly reduced in the cells treated with Ang II or TPA. This reduction of enzyme activity was also prevented by H7. These results indicate that Ang II inhibits ANP-induced cGMP accumulation in cultured glomerular mesangial cells through at least two mechanisms; one is the activation of calcium-dependent, calmodulin-stimulated cyclic nucleotide phosphodiesterase in the initial phase, and the other is the inhibition of guanylate cyclase resulting from protein kinase C activation in the maintenance phase.
为了评估血管收缩肽（血管紧张素II，Ang II）与血管舒张肽（心房利钠肽，ANP）之间的相互作用，我们研究了Ang II对培养的肾小球系膜细胞中ANP诱导的环磷酸鸟苷（cGMP）积累的影响。ANP迅速提高细胞内cGMP水平，在不存在异丁基甲基黄嘌呤（IBMX）的情况下，1分钟时刺激达到峰值；在存在IBMX的情况下，10分钟时达到峰值。当在不存在IBMX的情况下，细胞同时用Ang II和ANP处理1分钟时，ANP诱导的cGMP积累受到显著抑制。Ang II的这种抑制作用被IBMX完全消除，在无钙培养基中或用W7处理时显著降低，但不受H7影响。当细胞用A23187处理1分钟而不是用佛波酯（TPA）处理时，观察到类似的抑制作用。在存在IBMX的情况下，当在ANP刺激前15分钟用Ang II处理细胞时，Ang II抑制ANP诱导的cGMP积累。Ang II的这种抑制作用被H7阻断。在经Ang II或TPA处理的细胞中，ANP诱导的颗粒型鸟苷酸环化酶活性增加显著降低。这种酶活性的降低也被H7阻止。这些结果表明，Ang II通过至少两种机制抑制培养的肾小球系膜细胞中ANP诱导的cGMP积累；一种是在初始阶段激活钙依赖性、钙调蛋白刺激的环核苷酸磷酸二酯酶，另一种是在维持阶段由蛋白激酶C激活导致鸟苷酸环化酶受到抑制。
