Portal de Periódicos da CAPES

Non-competitive inhibition of myo-inositol transport in cultured bovine retinal capillary pericytes by glucose and reversal by Sorbinil

1986; Elsevier BV; Volume: 857; Issue: 2 Linguagem: Inglês

10.1016/0005-2736(86)90348-2

1879-2642

Weiye Li, Lawrence S. Chan, Mahin Khatami, John H. Rockey,

Aldose Reductase and Taurine

myo-Inositol transport by retinal capillary pericytes in culture was characterized. The major myo-inositol transport process was sodium-dependent, ouabain-sensitive, and saturable at 40 mM, indicating a carrier-mediated process. The sodium ion concentration required to produce one-half the maximal rate of myo-inositol uptake ([Na+]0.5) did not show dependence on the external myo-inositol concentration (22.3 mM sodium for 0.005 mM myo-inositol; 18.2 mM sodium for 0.05 mM myo-inositol). myo-Inositol transport was an energy-dependent, active process functioning against a myo-inositol concentration gradient. The kinetics of the sodium-dependent system fitted a 'velocity type' co-transport model where binding of sodium ion to the carrier increased the velocity (Vmax 28 to 313 pmol myo-inositol/μm DNA per 20 min when [Na+] varied from 9 to 150 mM) but not the affinity for myo-inositol (Km 0.92 to 0.83 mM when [Na+] varied from 9 to 150 mM). Metabolizable hexoses (d-glucose or d-galactose; greater than 5 mM) inhibited myo-inositol uptake. Dixon-plot analysis indicated that the inhibition was non-competitive with a Ki of 22.7 mM for d-glucose and 72.6 mM for d-galactose. The inhibition was significantly reversed by Sorbinil (0.1 mM), an aldose reductase inhibitor. In contrast, high concentrations of non-metabolizable hexoses (l-glucose, 3-O-methyl-d-glucose), or partially metabolizable 2-deoxy-d-glucose, did not significantly inhibit myo-inositol uptake. The inhibitory effect of d-glucose or d-galactose on myo-inositol transport appeared to be related to glucose or galactose metabolism via the polyol pathway.