The effect of azaserine upon the proline and methyl alpha-D-glucoside transport systems of rat renal brush-border membranes.
An inhibitory effect of azaserine on Na+ dependent proline and methyl alpha-D-glucoside transport of the rat renal brush-border membrane vesicles has been demonstrated. The inhibitory effects of azaserine were not the results of the drug disrupting the membrane vesicles as shown in osmolarity studies, nor did it affect the transport systems' affinities for Na+. Azaserine acts as a non-competitive inhibitor for the proline transport system in renal brush-border membranes by lowering 37% and 27% in the Vmax1 and Vmax2, respectively, when compared to that of control proline transport system. Azaserine had no effect upon the two Km values for proline uptake. Azaserine inhibition of methyl alpha-D-glucoside uptake by vesicles in the presence of 7.2 mM azaserine at 22 degrees C resulted in 66% increase in Km1 value and 44% decrease in Vmax1 as compared to that of control vesicles. There was no detectable effect upon the Km2 and Vmax2 of the methyl alpha-D-glucoside transport system. No effect of the drug was observed when sodium was equilibrated across the membrane, indicating that azaserine altered the driving force exerted by a sodium gradient. Azaserine only slightly affected the relative contribution of the two Km systems to total proline uptake. Contrary to the observed effect of azaserine upon the proline transport system, azaserine exerted a distinct effect upon the relative contribution to total uptake by the two Km systems in the low methyl alpha-D-glucoside concentration range. In the presence of 7.2 mM azaserine, the low-affinity, high-Km transport system becomes the major contributor to total methyl alpha-D-glucoside uptake by isolated renal brush-border vesicles.
D000818:Animals; D001377:Azaserine / Q000494:pharmacology*; D001693:Biological Transport, Active / Q000187:drug effects; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008757:Methylglucosides / Q000378:metabolism*; D008759:Methylglycosides / Q000378:metabolism*; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D009994:Osmolar Concentration; D011392:Proline / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism
D008757:Methylglucosides; D008759:Methylglycosides; C027020:methylglucoside; D001377:Azaserine; D011392:Proline; D012964:Sodium