title: Inhibition of aldose reductase: 13C NMR studies in isolated peripheral nerve.
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.
authors.affiliation: Department of Vascular Inflammatory & Musculoskeletal Research, Zeneca Pharmaceuticals, Macclesfield, Cheshire, UK.
authors.forename: J C
authors.initials: JC
authors.lastname: Waterton
authors.forename: S A
authors.initials: SA
authors.lastname: Breen
authors.forename: D J
authors.initials: DJ
authors.lastname: Mirrlees
authors.forename: C M
authors.initials: CM
authors.lastname: Sennitt
authors.forename: F
authors.initials: F
authors.lastname: Carey
mesh_terms: 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*
chemical_list: D002247:Carbon Isotopes; D004791:Enzyme Inhibitors; D009595:Nitroparaffins; D013450:Sulfones; D004376:Galactitol; C097934:ICI 222155; D000449:Aldehyde Reductase; D005690:Galactose