Effects of the slow calcium-channel blocker verapamil on phosphatic metabolism of crystalline lens

Abstract

The effects of calcium-channel blockade on phosphate metabolism in the rabbit lens ex vivo was studied using phosphorus-31 nuclear magnetic resonance (NMR) spectroscopy. Rates-of-change of the intralenticular pH and the following phosphatic metabolites in the lens were determined: ATP, ADP, inorganic orthophosphate, sugar phosphates, nucleoside diphosphosugars, phosphodiesters, dinucleotides, and an uncharacterized resonance peak at 6 delta in the 31P spectrum. Incubation in 20, 200 or 2000 micrograms/ml verapamil led to the same qualitative changes in the lens's metabolic profile at each different concentration; only the rates of metabolite change were altered significantly by verapamil concentration. Compared with the control, the entire orthophosphate resonance band increased relative to the signals of ATP, and the alpha-glycerophosphate and nucleoside monophosphate resonances increased in relation to inorganic orthophosphate, and these two resonance groups shifted relative to each other so that they coalesced, indicating that the two groups of signals arose from compounds in relatively different pH compartments. In addition to altering metabolic rates, verapamil reduced the intralenticular pH of the sugar phosphate and inorganic orthophosphate pools with respect to those containing the nucleoside monophosphates; the pH-change difference was about one order of magnitude smaller for the mononucleotide pool. Despite the metabolic alterations and changes in pH during verapamil incubation, lens clarity was unchanged.