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首页> 外文期刊>Cellular Physiology and Biochemistry >Regulation of adrenomedullin signaling in kidney interstitial fibroblasts
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Regulation of adrenomedullin signaling in kidney interstitial fibroblasts

机译：肾间质成纤维细胞中肾上腺髓质素信号传导的调节

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摘要

Adrenomedullin (AM), a potent vasodilatory peptide has beneficial effects in the kidney in vivo. The major aim of the present study was to determine the presence of AM receptor and the biological outcomes of AM on kidney interstitial fibroblasts in culture. Utilizing RT-PCR we found that NRK-49F cells express calcitonin receptor like receptor ( CRLR) and receptor activity modifying protein 2 (RAMP2) but not RAMP3. Treatment of these cells with AM resulted in a concentration-dependent increase in cAMP activation. The activation of adenylate cyclase system was enhanced by over-expression of CRLR, RAMP2 and RAMP3. Furthermore, AM-stimulated adenylate cyclase activity was inhibited by AM-[22-52] the AM receptor antagonist. AM also caused a PKA-dependent increase in CRE-luciferase activity. To test the biological consequences of AM treatment and the signaling pathways mediating them, we examined the effect of AM on proliferation of NRK-49F cells and the desensitization of AM receptor. AM caused a significant decrease in proliferation that was AM-receptor mediated but was PKA independent. In addition, AM also caused desensitization of cAMP response within a few minutes of treatment. This effect of AM was also not mediated via cAMP pathway as forskolin failed to desensitize AM receptor, and a PKA-inhibitor did not inhibit the desensitization. Taken together these results demonstrate that NRK-49F cells express functional AM receptor that when activated by AM results in a significant reduction of cell proliferation. Although cAMP activation by AM, as in other systems, is also observed in NRK-49F cells, PKA-independent pathways lead to some of the biological responses observed in these cells. Copyright (C) 2003 S. Karger AG, Basel. [References: 32]
机译：肾上腺髓质素（AM）是一种有效的血管扩张肽，在体内肾脏中具有有益作用。本研究的主要目的是确定AM受体的存在以及AM对培养的肾间质成纤维细胞的生物学结果。利用RT-PCR，我们发现NRK-49F细胞表达降钙素受体样受体（CRLR）和受体活性修饰蛋白2（RAMP2），但不表达RAMP3。用AM处理这些细胞会导致cAMP激活的浓度依赖性增加。 CRLR，RAMP2和RAMP3的过表达增强了腺苷酸环化酶系统的激活。此外，AM受体拮抗剂AM- [22-52]抑制了AM刺激的腺苷酸环化酶活性。 AM还引起CRE荧光素酶活性的PKA依赖性增加。为了测试AM治疗的生物学后果以及介导它们的信号传导途径，我们检查了AM对NRK-49F细胞增殖和AM受体脱敏的影响。 AM引起了AM受体介导但不依赖PKA的增殖显着降低。另外，AM在治疗的几分钟内还引起cAMP应答的脱敏。 AM的这种作用也未通过cAMP途径介导，因为佛司可林未能使AM受体脱敏，而PKA抑制剂也未抑制脱敏。综上所述，这些结果表明，NRK-49F细胞表达功能性AM受体，该受体在被AM激活时会导致细胞增殖的显着降低。尽管在NRK-49F细胞中也观察到AM激活cAMP，如在其他系统中一样，但PKA依赖性途径导致在这些细胞中观察到某些生物学反应。版权所有（C）2003 S.Karger AG，巴塞尔。 [参考：32]

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