Summary
n-Butyl-Biguanide inhibits sugar and amino-acid accumulation by renal cortex slices, without affecting the initial velocity of uptake of these substrates. Preincubation of the tissues in the presence of the drug provokes an inhibition of the initial velocity of uptake during a subsequent incubation. Since these results parallel those obtained with classical sodium-pump inhibitors, biguanides may cause a breakdown of the sodium gradient necessary for sugar and amino-acid transport.
The effects of biguanide are additive to those of ouabain, but not to those of ethacrynic acid. Furthermore, preincubation of tissues in a mixture of ouabain and biguanide or ethacrynic acid provokes a greater inhibition of initial uptake in a second incubation than does either inhibitor alone. Preincubation of tissues in a sodium-free medium containing biguanide has no effect on subsequent initial uptake of non-electrolytes.
Finally, biguanide is concentrated by renal tissue but does not inhibit Na+−K+-ATPase in renal microsomal preparations.
The results suggest an effect of biguanide on a second sodium pump, the locus of action being similar to that of ethacrynic acid.
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Robinson, J.W.L., Luisier, A.L. Inhibition of renal sugar and amino-acid transport by n-Butyl-Biguanide. Naunyn-Schmiedeberg's Arch. Pharmacol. 278, 23–34 (1973). https://doi.org/10.1007/BF00501860
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DOI: https://doi.org/10.1007/BF00501860