THE UPTAKE OF HEXAMETHONIUM-C14 BY KIDNEY SLICES

¹ Department of Pharmacology, State University of New York at Buffalo, Buffalo, New York

The mechanism of accumulation of hexamethonium-C¹⁴ by the kidney was studied by measuring its uptake by kidney cortical slices in vitro.

Kidney slices from cats accumulated hexamethonium-C¹⁴ from the incubation medium, and at a concentration of 10^-5 M, the slice-to-medium ratio for hexamethonium-C¹⁴ was about 12 after 6 hours of incubation. The maximum rate of uptake of hexamethonium-C¹⁴ by cat kidney slices was 0.8 µmol/g-hour at 10^-3 M hexamethonium. The accumulation was prevented by dinitrophenol and sodium azide. Mepiperphenidol, tetraethylammonium, and decamethonium also antagonized the uptake of hexamethonium-C-¹⁴. Kidney slices from immature cats were not able to accumulate hexamethonium-C¹⁴ as readily as slices from mature cats.

Slices from chicken kidneys also accumulated hexamethonium-C¹⁴ over a 6-hour period. The maximum rate of uptake by chicken slices was 0.4 µmol/g-hour at 10^-4 M hexamethonium.

Kidney slices from rabbits and rats were Unable to accumulate hexamethonium-C¹⁴ much above the medium concentration. The effect of altering hexamethonium concentration, pH, calcium concentration, potassium concentration, substrate, and region of kidney on accumulation of hexamethonium-C¹⁴ by cat and rabbit slices was compared. Optimal slice-to-medium ratios for cat kidney were obtained with slices from the cortex, at 10^-5 M hexamethonium, at pH 7.4, in 1.25 mM Ca⁺⁺, in 5 mM K⁺, and with acetate as the substrate. The maximum slice-to-medium ratios for rabbit kidney were obtained at 10^-7 M hexamethonium, at pH 8.0, in 5 mM K⁺, with no calcium, and with acetate as the substrate. Even so, the ratios with rabbit slices were usually very low.

It is suggested that hexamethonium is concentrated by cat and chicken kidney slices by an active process, and that the renal tubular transport system for organic bases may participate in its accumulation. It is further suggested that once inside the tubular cell, hexamethonium is bound to some cellular constituent.

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