Exposure of rat isolated stomach and rats in vivo to [(14)C]agmatine: accumulation in the stomach wall and distribution in various tissues.
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.
Molderings
Gerhard J
GJ
Institut für Pharmakologie und Toxikologie, Universität Bonn, Reuterstr. 2b, D-53113 Bonn, Germany. molderings@uni-bonn.de
Heinen
Anja
A
Menzel
Sigrid
S
Göthert
Manfred
M
D000284:Administration, Oral; D000376:Agmatine / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D000818:Animals; D002250:Carbon Radioisotopes; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000378:metabolism; D066298:In Vitro Techniques; D007408:Intestinal Absorption; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000187:drug effects*; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D000376:Agmatine