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鲑鱼降钙素与人体肾脏中cGMP的产生:体内和体外研究

Salmon calcitonin and cGMP production by human kidney: studies in vivo and in vitro.

作者信息

Gennari C, Toccafondi R, Rotella C M, Francini G, Brandi M L, Maioli E

出版信息

Calcif Tissue Int. 1983 May;35(3):273-8. doi: 10.1007/BF02405045.

Abstract

In order to evaluate whether or not the action of salmon calcitonin (sCT) at the kidney level could be mediated through specific receptors for the hormone, we have studied the effects of sCT infusions on urinary excretion of cyclic nucleotides in humans. Parallel in vitro studies have been conducted by evaluating the effects of sCT on cyclic nucleotide levels in primary cultures of cortical and medullary human kidney cells. In vivo experiments showed that sCT induced an increase in cGMP in human urine, which was rapid and short-lasting, being superimposable on the increase of urinary excretion of calcium and magnesium. The increase of inorganic phosphate urinary excretion was delayed and appeared to parallel that of urinary cAMP. On the other hand, our in vitro experiments showed that sCT stimulated the guanylate cyclase-cGMP system of human kidney cortical cells at nanomolar concentrations, while higher concentrations of the hormone were required to activate the adenylate cyclase-cAMP system. In addition, sCT was not able to significantly modify the cellular levels of either nucleotide in human kidney medullary cells. Present data demonstrated a direct effect of sCT on human kidney cortical cGMP production, while the efficacy of sCT on the kidney cortex adenylate cyclase-cAMP system appears to be delayed and/or reduced.

摘要

为了评估鲑鱼降钙素(sCT)在肾脏水平的作用是否可通过该激素的特异性受体介导,我们研究了sCT输注对人体尿中环核苷酸排泄的影响。通过评估sCT对人肾皮质和髓质细胞原代培养物中环核苷酸水平的影响,进行了平行的体外研究。体内实验表明,sCT可使人体尿液中的cGMP迅速短暂增加,这与钙和镁的尿排泄增加叠加。无机磷酸盐尿排泄的增加延迟出现,似乎与尿cAMP的增加平行。另一方面,我们的体外实验表明,sCT在纳摩尔浓度下刺激人肾皮质细胞的鸟苷酸环化酶-cGMP系统,而激活腺苷酸环化酶-cAMP系统则需要更高浓度的该激素。此外,sCT不能显著改变人肾髓质细胞中任何一种核苷酸的细胞水平。目前的数据表明sCT对人肾皮质cGMP产生有直接作用,而sCT对肾皮质腺苷酸环化酶-cAMP系统的作用似乎延迟和/或减弱。

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