Structural requirement for axonal regeneration-promoting effect of polyamines in cultured rat hippocampal neurons.
We have previously found that spermine, spermidine and putrescine promote axonal regeneration following axotomy in cultured rat hippocampal neurons. In the present study, we investigated which part of the polyamine molecule is responsible for the regeneration-promoting effect. Testing the effects of several synthetic analogues revealed that the butanediamine moiety is essential for the activity and the terminal primary amines are necessary for full agonist activity. The structure-activity relationship indicates that the regeneration-promoting effects of polyamines are not associated with NMDA receptors.
Abe
K
K
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, The University of Tokyo, Japan.
Chu
P
P
Shirahata
A
A
Samejima
K
K
Saito
H
H
D000818:Animals; D001369:Axons / Q000502:physiology*; D019771:Axotomy; D002103:Cadaverine / Q000494:pharmacology; D002478:Cells, Cultured; D003959:Diamines / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology*; D009416:Nerve Regeneration / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000648:ultrastructure; D010880:Piperidines / Q000494:pharmacology; D011073:Polyamines / Q000494:pharmacology*; D011700:Putrescine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013096:Spermine / Q000031:analogs & derivatives / Q000494:pharmacology
D003959:Diamines; D010880:Piperidines; D011073:Polyamines; D013096:Spermine; C017921:norspermine; C009475:trimethylenediamine; D002103:Cadaverine; D011700:Putrescine