Inhibition of aldose reductase: 13C NMR studies in isolated peripheral nerve |
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Authors: | JC Waterton SA Breen DJ Mirrlees CM Sennitt F Carey |
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Affiliation: | Department of Vascular Inflammatory & Musculoskeletal Research, Zeneca Pharmaceuticals, Macclesfield, Cheshire, UK. |
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Abstract: | We report 13C NMR measurements of the flux through aldose reductase in isolated rat sciatic nerve, and its inhibition by an aldose reductase inhibitor of the sulphonylnitromethane class. 1-13C] galactose was used as substrate, and the rate of production of 1-13C] dulcitol was measured. Quantitation required the use both of internal extracellular, and external, standards. The mean net forward flux (+/- SD) was 20 +/- 11 nmol/(mL nerve water)/min (n = 10). In the presence of the inhibitor, flux was reduced significantly (p < 0.001) to 13% of control. Since dulcitol is symmetrical, an estimate of the backward flux, to 6-13C] galactose, is also possible; under our conditions, this was negligible. |
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