The natriuretic peptides (NPs) B-type NP (BNP) and urodilatin (URO) exert renal protective properties via the participate guanylyl cyclase A receptor (pGC-A). As a potential renal-enhancing strategy, we engineered a novel designer peptide that we call CRRL269. CRRL269 was investigated in human cell lines and in normal canines to define potential cardiorenal enhancing actions. The mechanism of its cardiorenal selective properties was also investigated. In vitro NP receptor activity was quantified with guanosine 35'-cyclic monophosphate generation. In vivo effects were determined in normal canine acute infusion studies. We observed that CRRL269 demonstrated enhanced pGC-A activity in renal compared with nonrenal cell lines. CRRL269 exerted enhanced resistance to neprilysin compared with URO.
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机译:利钠肽 (NPs) B 型 NP (BNP) 和尿氨酸蛋白 (URO) 通过参与鸟苷酸环化酶 A 受体 (pGC-A) 发挥肾脏保护特性。作为一种潜在的肾脏增强策略,我们设计了一种我们称之为CRRL269的新型设计肽。在人类细胞系和正常犬科动物中研究了CRRL269以确定潜在的心肾增强作用。还研究了其心肾选择特性的机制。体外NP受体活性通过鸟苷35'-环磷酸生成量化。在正常犬急性输注研究中确定了体内效应。我们观察到,与非肾细胞系相比,CRRL269在肾脏中表现出增强的pGC-A活性。与URO相比,CRRL269对脑啡肽酶的耐药性增强。
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