Pharmacological characteristics of the specific transporter for the endogenous cell growth inhibitor agmatine in six tumor cell lines.
OBJECTIVE
This study examined agmatine transport into six human intestinal tumor cell lines and compared the pharmacological properties of this transporter with those of the agmatine carrier previously characterized in human glioblastoma cells.


METHODS
Carrier-mediated uptake was determined as specific accumulation of [(14)C]agmatine in the cells. The changes in intracellular agmatine concentration in the tumor cells after 24 h incubation with 1 mM agmatine was analyzed by high-performance liquid chromatography.


RESULTS
Specific [(14)C]agmatine accumulation was found in the six human intestinal tumor cell lines Caco2, Cx1, Colo320, HT29, Colo205E, and SW480. Specific [(14)C]agmatine accumulation was inhibited by phentolamine, putrescine, spermine, clonidine, and decynium-22 but not by corticosterone, O-methylisoprenaline, or l-carnitine. Incubation with exogenous agmatine for 24 h increased intracellular agmatine content in all cell lines by a multiple of the basal endogenous content. Transfection of HEK293 cells with cDNA encoding either hOCT1, hOCT2, or hOCT3 did not enhance [(14)C]agmatine accumulation compared to nontransfected cells.


CONCLUSIONS
All intestinal tumor cell lines investigated express a functional specific agmatine transporter which exhibit pharmacological characteristics similar to those of the agmatine transporter in glioblastoma cells. This agmatine carrier is not identical with any so far known organic cation transport system.
Heinen
A
A
Institute of Pharmacology and Toxicology, University of Bonn, Reuterstrasse 2b, 53113, Bonn, Germany.
Brüss
M
M
Bönisch
H
H
Göthert
M
M
Molderings
G J
GJ
D000376:Agmatine / Q000493:pharmacokinetics*; D026905:Amino Acid Transport Systems; D001932:Brain Neoplasms / Q000473:pathology; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D018076:DNA, Complementary; D005770:Gastrointestinal Neoplasms / Q000473:pathology*; D005909:Glioblastoma / Q000473:pathology; D006801:Humans; D014162:Transfection; D014407:Tumor Cells, Cultured
D026905:Amino Acid Transport Systems; D002250:Carbon Radioisotopes; D018076:DNA, Complementary; D000376:Agmatine