title: Stimulation of renin secretion by ethacrynic acid is independent of Na(+)-K(+)-2Cl- cotransport.
abstract: This study investigated the cellular mechanism of stimulation of renin secretion by the loop diuretic ethacrynic acid (EA) in rabbit renal cortical slices. The diuretic rapidly stimulated renin secretion reversibly and in a concentration-dependent manner. The stimulation was independent of the presence of Na+, Cl-, Ca2+, or other loop diuretics (furosemide and bumetanide) in the incubation media, suggesting that the stimulation in vitro was not dependent on the inhibitory effect of the diuretic on Na(+)-K(+)-2Cl-cotransport. The findings do not support the macula densa hypothesis. The stimulation by the diuretic was prevented and reversed by thiols such as cysteine and dithiothreitol, which also prevented and reversed the stimulation of renin secretion by the nondiuretic sulfhydryl reagent P-chloromercuriphenyl-sulfonate (PCMPS). These results suggest that EA stimulates renin secretion in vitro via reversible chemical reactions with specific membrane sulfhydryl groups that may have no functional role in the Na(+)-K(+)-2Cl- cotransport.
authors.affiliation: Department of Physiology, University of Massachusetts Medical School, Worcester 01655.
authors.forename: C S
authors.initials: CS
authors.lastname: Park
authors.forename: P S
authors.initials: PS
authors.lastname: Doh
authors.forename: R E
authors.initials: RE
authors.lastname: Carraway
authors.forename: G G
authors.initials: GG
authors.lastname: Chung
authors.forename: J C
authors.initials: JC
authors.lastname: Fray
authors.forename: T B
authors.initials: TB
authors.lastname: Miller
mesh_terms: D002731:4-Chloromercuribenzenesulfonate / Q000494:pharmacology; D000818:Animals; D002034:Bumetanide / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D004976:Ethacrynic Acid / Q000494:pharmacology*; D005665:Furosemide / Q000494:pharmacology; D066298:In Vitro Techniques; D007477:Ions; D009994:Osmolar Concentration; D011817:Rabbits; D012083:Renin / Q000378:metabolism*; D028021:Sodium-Potassium-Chloride Symporters; D013438:Sulfhydryl Compounds / Q000494:pharmacology; D013997:Time Factors
chemical_list: D002352:Carrier Proteins; D007477:Ions; D028021:Sodium-Potassium-Chloride Symporters; D013438:Sulfhydryl Compounds; D002034:Bumetanide; D002731:4-Chloromercuribenzenesulfonate; D005665:Furosemide; D012083:Renin; D004976:Ethacrynic Acid