Dynamic changes in the organophosphate profile upon treatment of the crystalline lens with dexamethasone

Dynamic changes in organophosphate metabolites during incubations of the intact crystalline lens in a medium containing 2 X 10(-3) M dexamethasone were studied using phosphorus-31 nuclear magnetic resonance intact-tissue spectroscopy. ATP, ADP, inorganic orthophosphate, alpha-glycerophosphate, nicotinamide adenine dinucleotides, uridine diphosphorylglucose and diphosphorylgalactose, glycerol 3-phosphorylethanolamine and -phosphorylcholine, and an unidentified phosphorus-containing molecule at 6 ppm were quantitated. Time-dependent changes in lens metabolism involving these compounds were examined during a 24-hr incubation period with dexamethasone. The first event in the decline of the tissue after steroid incubation was the consumption of ATP, which was linear with time until the ATP was reduced to 10% of its initial value. The sugar phosphates, inorganic orthophosphate, and the nucleoside diphosphorylsugars increased linearly with time, whereas the dinucleotides decreased. The ADP concentration was unaffected by the steroid treatment, as was that of the other organophosphates in the intact tissue profile. The steroid-induced alterations in lens phosphate metabolite levels follow a distinctive pattern that differs substantially from that observed in response to experimental hypoglycistic or hyperglycistic conditions. These findings suggest that pharmacologic steroid doses may directly alter lens metabolism through a complex mechanism involving, at least in part, a steroid-mediated antagonism of lens glucose uptake and/or utilization.