Inhibition of aldose reductase: 13C NMR studies in isolated peripheral nerve.
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.
Waterton
J C
JC
Department of Vascular Inflammatory & Musculoskeletal Research, Zeneca Pharmaceuticals, Macclesfield, Cheshire, UK.
Breen
S A
SA
Mirrlees
D J
DJ
Sennitt
C M
CM
Carey
F
F
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D002247:Carbon Isotopes; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004376:Galactitol / Q000032:analysis / Q000378:metabolism; D005690:Galactose / Q000378:metabolism; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009595:Nitroparaffins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000201:enzymology*; D013450:Sulfones / Q000494:pharmacology*
D002247:Carbon Isotopes; D004791:Enzyme Inhibitors; D009595:Nitroparaffins; D013450:Sulfones; D004376:Galactitol; C097934:ICI 222155; D000449:Aldehyde Reductase; D005690:Galactose