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Ribozyme compromise of adrenomedullin mRNA reveals a physiological role in the regulation of water intake.

机译:肾上腺髓质素mRNA的核酶危害揭示了在调节饮水量中的生理作用。

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摘要

The adrenomedullin (AM) preprohormone is posttranslationally processed to result in two biologically active fragments, AM and proadrenomedullin NH(2)-terminal 20 peptide (PAMP). AM is thought to play a role in fluid and electrolyte balance by acting in brain to inhibit salt and water appetite and in the kidney to cause diuresis and natriuresis. We previously have shown that AM is necessary for the short-term regulation of salt intake. In this paper, we have designed a ribozyme, a catalytic RNA molecule, which specifically recognizes and cleaves the AM transcript. In cultured vascular smooth muscle cells, ribozyme treatment lowered AM mRNA and reduced peptide content. Intracerebroventricular administration of the ribozyme lowered hypothalamic AM content and led to an exaggerated drinking response in rats, demonstrating that endogenous, brain-derived AM is physiologically relevant and necessary for short-term control of water intake.
机译:肾上腺髓质素(AM)前激素被翻译后处理,以产生两个生物活性片段,AM和肾上腺髓质素NH(2)-末端20肽(PAMP)。 AM被认为通过在大脑中抑制盐和水的食欲,并在肾脏中引起利尿和利钠作用,在体液和电解质平衡中发挥作用。先前我们已经表明,AM对于短期调节盐摄入量是必需的。在本文中,我们设计了一种核酶,一种催化性RNA分子,可以特异性识别和切割AM转录物。在培养的血管平滑肌细胞中,核酶处理可降低AM mRNA并降低肽含量。脑室内给予核酶可降低大鼠下丘脑AM含量,并导致大鼠饮酒反应过度,表明内源性脑源性AM在生理上是相关的,对于短期控制摄水量是必需的。

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