Department of Physiology, Institute for Medical Sciences, Center for Healthcare Technology Development, Chonbuk National University Medical School, Jeonju 561-180, Republic of Korea.
Peptides. 2012 Jan;33(1):59-66. doi: 10.1016/j.peptides.2011.12.006. Epub 2011 Dec 17.
Dendroaspis natriuretic peptide (DNP) is one of four members of the natriuretic peptide family sharing functional and structural properties. The purpose of the present study was to elucidate the physiological role of DNP on renal functions and its cellular mechanism in the rabbit kidney. DNP (5 μg/kg/min) infused intravenously increased urine volume and urinary excretion of electrolytes. These renal actions induced by DNP were more pronounced than those caused by atrial natriuretic peptide (ANP). We compared profiles of (125)I-ANP and (125)I-DNP by reverse-phase HPLC during incubation in rabbit plasma at 37°C for 1, 2, and 4h. While (125)I-ANP was quickly degraded within 1h, (125)I-DNP was still stable in plasma for 4h. DNP induced the greatest cyclic guanosine monophosphate (cGMP) production in the glomeruli in a dose-dependent manner, when compared to other renal structures including cortical tubules, outer medullary tubules, and inner medullary tubules. Affinity cross-linking analysis revealed NPR-A is selective receptor for DNP in glomeruli. Forskolin, a stimulator of adenylyl cyclase, significantly decreased cGMP production in the renal glomeruli but not in the renal medulla. In summary, DNP is a more effective activator of renal functions than ANP, possibly because of the degradation resistance of DNP against the endogenous peptidases in plasma or tissues. These findings suggest that DNP plays a pivotal role as a renal regulating peptide via specific natriuretic peptide receptors with a guanylyl cyclase domain.
树眼镜蛇利尿钠肽（DNP）是具有功能和结构特性的利钠肽家族的四个成员之一。本研究的目的是阐明 DNP 对肾功能的生理作用及其在兔肾中的细胞机制。静脉内输注 DNP（5μg/kg/min）可增加尿量和电解质的尿排泄。与心钠肽（ANP）相比，DNP 引起的这些肾脏作用更为明显。我们比较了（125）I-ANP 和（125）I-DNP 在兔血浆中于 37°C 孵育 1、2 和 4h 时的反相 HPLC 图谱。虽然（125）I-ANP 在 1h 内迅速降解，但（125）I-DNP 在血浆中仍稳定 4h。与包括皮质小管、外髓质小管和内髓质小管在内的其他肾结构相比，DNP 以剂量依赖性方式诱导肾小球中环鸟苷酸（cGMP）产生最大。亲和交联分析表明 NPR-A 是肾小球中 DNP 的选择性受体。佛司可林，一种腺苷酸环化酶的刺激物，显著降低肾肾小球中的 cGMP 产生，但不降低肾髓质中的 cGMP 产生。总之，DNP 是一种比 ANP 更有效的肾功能激活剂，可能是因为 DNP 对血浆或组织内内源性肽酶具有降解抗性。这些发现表明 DNP 通过具有鸟苷酸环化酶结构域的特定利钠肽受体发挥作为肾调节肽的关键作用。
