Modulating effect of thiol-disulfide status on [14C]aminopyrine accumulation in the isolated parietal cell.
Thiol-oxidizing agents were found to stimulate [14C] aminopyrine accumulation, a reliable index of acid secretory function of isolated canine parietal cells. Glutathione is the predominant intracellular free thiol; thus, its oxidation status largely determines the thiol-disulfide status of the cell by thiol-disulfide interchange reactions. Three agents which alter glutathione oxidation status by different mechanisms were applied to parietal cells in vitro to investigate whether enhanced formation of GSSG alters acid secretory function. The agents studied were diamide (which nonenzymatically oxidizes GSH to GSSG), tert-butyl hydroperoxide (an organic peroxide specifically reduced by glutathione peroxidase, thereby generating GSSG for GSH), and 1,3-bis(2-chloroethyl)-1-nitrosourea (an inhibitor of NADPH:GSSG reductase, which presumably allows the accumulation of GSSG). Each of these agents stimulated aminopyrine accumulation in a dose-dependent fashion. Simple depletion of GSH by diethyl maleate or 2-cyclohexene-1-one did not stimulate aminopyrine accumulation. Likewise, enhanced aminopyrine accumulation occurred at diamide concentrations which did not cause significant depletion of total cellular glutathione. The thiol-reducing agent, dithiothreitol, prevented enhanced aminopyrine accumulation by 1,3-bis(2-chloroethyl)-1-nitrosourea and tert-butyl hydroperoxide. These observations support the hypothesis that thiol-disulfide interchange reactions involving GSSG modulate the acid secretory function of the isolated parietal cell.
D000632:Aminopyrine / Q000378:metabolism*; D000818:Animals; D002330:Carmustine / Q000494:pharmacology; D003512:Cyclohexanones / Q000494:pharmacology; D003958:Diamide / Q000494:pharmacology; D004229:Dithiothreitol / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005744:Gastric Acid / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D008298:Maleates / Q000494:pharmacology; D010295:Parietal Cells, Gastric / Q000187:drug effects / Q000378:metabolism*; D010545:Peroxides / Q000494:pharmacology; D013439:Sulfhydryl Reagents / Q000494:pharmacology*; D020122:tert-Butylhydroperoxide
D003512:Cyclohexanones; D008298:Maleates; D010545:Peroxides; D013439:Sulfhydryl Reagents; D000632:Aminopyrine; D003958:Diamide; C028215:2-cyclohexen-1-one; D020122:tert-Butylhydroperoxide; C014476:diethyl maleate; D005978:Glutathione; D004229:Dithiothreitol; D002330:Carmustine