The Presence of an Na+/Spermine Antiporter in the Rat Renal Brush-border Membrane

• Published in: Journal of pharmacy and pharmacology Vol. 51; no. 3; pp. 279 - 284
• Main Authors: KOBAYASHI, MICHIYA, FUJISAKI, HIROKO, SUGAWARA, MITSURU, ISEKI, KEN, MIYAZAKI, KATSUMI
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-03-1999; Pharmaceutical Press
• Subjects: Animals; Antiporters - physiology; Biological and medical sciences; Cell physiology; Drug Interactions; Fundamental and applied biological sciences. Psychology; In Vitro Techniques; Kidney Tubules - physiology; Membrane and intracellular transports; Microvilli - chemistry; Microvilli - metabolism; Molecular and cellular biology; Polyamines - pharmacokinetics; Rats; Rats, Wistar; Sodium - chemistry; Spermine - pharmacokinetics; Temperature; Trientine - pharmacokinetics; Sodium Ions; Intracellular transport; Polyamine; Rat; Transportation system; Trientine; Rodentia; In vitro; Kidney; Vertebrata; Brush border; Mammalia; Spermine; Animal; Mechanism of action; Proximal tube
• ISSN: 0022-3573; 2042-7158
• DOI: 10.1211/0022357991772457

This study was aimed at determining the driving force for spermine transport in rat renal proximal tubular brush‐border membrane.
The uptake of spermine and trientine, a spermine‐like drug used for treating Wilson's disease, into rat renal brush‐border membrane vesicles was significantly stimulated by an outwardly directed Na+ gradient. The Na+‐dependent uptake was temperature dependent and saturable. A kinetic analysis of the initial uptake of spermine with an Na+ gradient gave a Km value of 1.44μM and a Vmax value of 6.31pmol (mg protein)‐1 /30 s. The Na+‐ dependent uptake of [3H]spermine was inhibited by spermine, trientine and tetraethylenepentamine. Substrates of the H+/organic cation transporter (cimetidine and tetraethylammonium), physiological polyamines (putrescine and spermidine) with 2 or 3 amino groups and aminoglycosides (amikacin and tobramicin) with 4 or 5 cationic amines did not affect the uptake of spermine in the presence of an outwardly directed Na+ gradient.
These results suggest that the renal tubular secretion of spermine is mediated by an Na+/spermine antiport system which is specific for a straight‐chain polyamine compound with more than 4 amino groups.