Control of spermidine and spermine levels in rat tissues by trans-4-methylcyclohexylamine, a spermidine-synthase inhibitor.
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 mumol 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.
Kobayashi
Masaki
M
Faculty of Pharmaceutical Sciences, Josai University, Sakado, Japan.
Watanabe
Toshiko
T
Xu
Yong Ji
YJ
Tatemori
Minoru
M
Goda
Hitomi
H
Niitsu
Masaru
M
Shirahata
Akira
A
Samejima
Keijiro
K
D000475:Alkenes / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D003514:Cyclohexylamines / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004334:Drug Administration Schedule; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D051381:Rats; D013095:Spermidine / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D011436:Spermidine Synthase / Q000037:antagonists & inhibitors*; D013096:Spermine / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D015854:Up-Regulation; D015431:Weight Loss / Q000187:drug effects
C503069:5-amino-1-pentene; D000475:Alkenes; D003514:Cyclohexylamines; D013096:Spermine; C059116:4-methylcyclohexylamine; D011436:Spermidine Synthase; D013095:Spermidine