Control of Spermidine and Spermine Levels in Rat Tissues by trans-4-Methylcyclohexylamine, a Spermidine-Synthase Inhibitor

• Published in: Biological & Pharmaceutical Bulletin Vol. 28; no. 4; pp. 569 - 573
• Main Authors: Kobayashi, Masaki, Watanabe, Toshiko, Xu, Yong Ji, Tatemori, Minoru, Goda, Hitomi, Niitsu, Masaru, Shirahata, Akira, Samejima, Keijiro
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01.04.2005; Pharmaceutical Society of Japan; Japan Science and Technology Agency
• Subjects: 15N-labelled polyamine; Alkenes - administration & dosage; Alkenes - pharmacology; Animals; Cyclohexylamines - administration & dosage; Cyclohexylamines - pharmacology; Dose-Response Relationship, Drug; Down-Regulation; Drug Administration Schedule; Gene Expression Regulation - drug effects; inhibitor; ionspray ionization-mass spectrometry; Male; oral administration; putrescine aminopropyltransferase; Rats; Spermidine - administration & dosage; Spermidine - metabolism; Spermidine - pharmacology; Spermidine Synthase - antagonists & inhibitors; Spermine - administration & dosage; Spermine - metabolism; Spermine - pharmacology; spermine : spermidine ratio; Up-Regulation; Weight Loss - drug effects
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.28.569

In rat tissues, a decrease in spermidine, accompanied by an increase in spermine was induced by the oral administration (once daily for either 1 week or 1 month) of trans-4-methylcyclohexylamine (4MCHA), a spermidine synthase inhibitor. This is similar to the changes observed in polyamine content when cell growth is arrested. The body-weight gain of the rats tended to decrease with increasing doses of 4MCHA. A decrease in spermidine, combined with a moderate increase in spermine, was observed dose-dependently in all of the tissues tested, with a relatively fast clearance of 4MCHA. Manipulating the polyamine content of tissues, by daily administration of 100 μmol 4MCHA for 1 week, made it possible to estimate the effects of simultaneously added spermidine or spermine on endogenous polyamine contents. The altered polyamine levels, obtained after daily administration for 1 week, were maintained during the extended 1-month period, with growth-dependent alteration. The results show it is possible to produce experimental rats with a higher spermine:spermidine ratio than control rats to investigate the physiological significance of spermidine downregulation and spermine upregulation in vivo.