Cellular mechanism of stimulation of renin secretion by the mercurial diuretic mersalyl.
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.
Park
C S
CS
Department of Physiology, University of Massachusetts Medical School, Worcester 01655.
Doh
P S
PS
Lee
C J
CJ
Han
D S
DS
Carraway
R E
RE
Miller
T B
TB
D002731:4-Chloromercuribenzenesulfonate / Q000494:pharmacology; D000818:Animals; D002712:Chlorides / Q000378:metabolism; D003545:Cysteine / Q000494:pharmacology; D004976:Ethacrynic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000378:metabolism; D008634:Mersalyl / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D011817:Rabbits; D012083:Renin / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D013268:Stimulation, Chemical
D002712:Chlorides; D008634:Mersalyl; D002731:4-Chloromercuribenzenesulfonate; D012964:Sodium; D012083:Renin; D003545:Cysteine; D004976:Ethacrynic Acid; D011188:Potassium