The authors report on (1) the absorption of agmatine from the gastrointestinal tract as an important source of this polycation in the organism, (2) its organ distribution, and (3) its putative role in liver regeneration. When rats received 0.5 microCi [(14)C]agmatine contained in 5 grams of standard rat chow after a fasting period of 24 hours, radioactivity was recovered in all organs investigated, in blood, and in urine. In the liver 67% +/- 7% of administered radioactivity was found. After partial (two-thirds) hepatectomy, administration of 250 mg and 500 mg agmatine by gavage for 6 days reduced liver regeneration at day 7 by 20% and 22%, respectively, compared with animals that received no agmatine. Agmatine is absorbed from the gastrointestinal tract, probably by means of a specific transporter. It is likely that agmatine in the chyme of the gut represents an essential source of agmatine in the tissues of the organism. An increase in the availability of gastrointestinal agmatine for absorption impairs liver regeneration and may contribute to the development of liver diseases.

The aims of the present study were: (i) to investigate the accumulation of radioactivity in the stomach wall after luminal exposure of the rat isolated stomach to[(14)C]agmatine and (ii) to determine the distribution of radioactivity in various tissues after oral administration of this radiolabelled polyamine to rats in vivo. In isolated rat stomach, [(14)C]agmatine was accumulated in part by an energy-dependent uptake process that could be inhibited by phentolamine. These findings correspond to properties of the recently identified specific agmatine transporter in human glioma cells, suggesting that in rat stomach [(14)C]agmatine is taken up by such a carrier. In in vivo experiments, rats received 0.5 microCi [(14)C]agmatine adsorbed to 5 g rat standard chow after a fasting period of 24 h. After oral ingestion of [(14)C]agmatine, radioactivity was recovered in all organs investigated as well as in blood and urine. Radioactivity also seemed to be secreted into the pancreaticobiliary fluid, as it was recovered in the luminal content of distal ileum and sigmoid colon. Accumulation of radioactivity in organs and distal gut luminal content was dose-dependently decreased by simultaneous administration of putrescine. In conclusion, the present data are compatible with the view that agmatine can be absorbed in rat at least from the stomach and probably also from the gut by means of an energy-dependent agmatine transport mechanism. Agmatine itself and/or its degradation products, which also have the potential to be pharmacologically active, are unevenly distributed between the organs. Putative secretion of radioactivity into the pancreaticobiliary fluid suggests the potential for an enterohepatic circulation of agmatine. In view of the high intraluminal concentration of agmatine in the stomach and distal gut and the operation of an agmatine transporter, it is rather likely that agmatine in the chyme of the gut represents an important source for agmatine detected in the tissues of the organism.

No abstract

BACKGROUND.The polyamine system is a promising target for anticancer therapy.Ideally, an antineoplastic compound affecting this system should inhibit both ornithine decarboxylase and the polyamine transporter, and toxicity should be mild. Agmatine, decarboxylated L-arginine, appears to be such a compound. METHODS.Adenosine triphosphate levels and the protein content of cell populations in culture were identified as surrogate markers for cell count. Agmatine content in cells and tissue specimens was measured by high-performance liquid