Park C S, Doh P S, Lee C J, Han D S, Carraway R E, Miller T B
Department of Physiology, University of Massachusetts Medical School, Worcester 01655.
J Pharmacol Exp Ther. 1991 Apr;257(1):219-24.
The aim of the present study was to elucidate the cellular mechanism by which the mercurial diuretic mersalyl stimulates renin secretion in rabbit renal cortical slices in vitro. The stimulatory effect of mersalyl on renin secretion was rapid, reversible and concentration dependent. The stimulation was not dependent on the presence of ions such as Na+, Cl- and Ca++, and it was unaffected by inhibitors of Na+/K+/2Cl- cotransport, such as bumetanide and furosemide. However, the stimulation was blocked and reversed by thiols, such as L-cysteine and dithiothreitol. Furthermore, the maximal stimulatory effect of mersalyl on renin secretion was not additive to that produced by the non-diuretic mercurial sulfhydryl reagent P-chloromercuriphenylsulfonate nor to that produced by the non-mercurial diuretic sulfhydryl reagent, ethacrynic acid. These results support the hypothesis that mersalyl stimulates renin secretion by forming a reversible mercaptide bond with sulfhydryl groups, located perhaps on the plasma membrane of juxtaglomerular cells. These particular sulfhydryl groups appear to have no functional role in the diuretic action of mersalyl.
本研究的目的是阐明汞利尿剂汞撒利在体外刺激兔肾皮质切片中肾素分泌的细胞机制。汞撒利对肾素分泌的刺激作用迅速、可逆且浓度依赖性。该刺激不依赖于Na +、Cl - 和Ca ++ 等离子的存在,并且不受Na+/K+/2Cl - 协同转运抑制剂(如布美他尼和呋塞米)的影响。然而,该刺激被硫醇(如L - 半胱氨酸和二硫苏糖醇)阻断并逆转。此外,汞撒利对肾素分泌的最大刺激作用与非利尿剂汞巯基试剂对氯汞苯磺酸盐或非汞利尿剂巯基试剂依他尼酸产生的刺激作用不具有相加性。这些结果支持以下假设:汞撒利通过与可能位于球旁细胞膜上的巯基形成可逆的硫醇盐键来刺激肾素分泌。这些特定的巯基似乎在汞撒利的利尿作用中没有功能作用。