Polyamines antagonize N-methyl-D-aspartate-evoked depolarizations, but reduce Mg2+ block.
This study utilized a grease-gap preparation to investigate the effects of polyamines on responses of CA1 hippocampal pyramidal cells to N-methyl-D-aspartate (NMDA) and on the block of the NMDA channel by Mg2+. In the absence of added Mg2+, 1,10-diaminodecane (0.1-1 mM) non-competitively antagonized NMDA-evoked depolarizations. Its antagonism slowly progressed to a stable value, was not use-dependent and did not reverse completely upon washout. Similar results were obtained with 100 microM spermine and 1 mM diethylenetriamine. Addition of 1 mM Mg2+ to the superfusion medium greatly reduced these effects. Conversely, the polyamines attenuated the blocking action of Mg2+. Postnatal treatment with alpha-difluoromethylornithine reduced the total polyamine content of area CA1 in 10- to 15-day-old rats almost to the adult level (although spermine content was unaffected). Mg2+ less potently antagonized NMDA-evoked depolarizations in slices from 10- to 15-day-old rats than in slices from adult rats, and this difference was unaffected by the alpha-difluoromethylornithine treatment. These results suggest (1) that there are rapid and slow components to the antagonism of NMDA-evoked depolarizations by polyamines, both of which may involve permeation of the polyamine into or through the NMDA channel: (2) that polyamine release in brain could modulate the Mg2+ sensitivity of responses to NMDA; and (3) that changes in the total content of endogenous polyamine do not explain developmental differences in the sensitivity of NMDA-evoked depolarizations to Mg2+.
Bowe
M A
MA
Department of Pharmacology, Duke University Medical Center, Durham, NC 27710, USA.
Nadler
J V
JV
D000200:Action Potentials / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D001667:Binding, Competitive; D002851:Chromatography, High Pressure Liquid; D003959:Diamines / Q000494:pharmacology*; D004347:Drug Interactions; D000518:Eflornithine / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D008274:Magnesium / Q000494:pharmacology*; D008297:Male; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D010622:Phencyclidine / Q000031:analogs & derivatives / Q000378:metabolism; D011073:Polyamines / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000166:cytology / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013096:Spermine / Q000494:pharmacology*
C065351:1,10-diaminodecane; D003959:Diamines; D011073:Polyamines; C005391:diethylenetriamine; D013096:Spermine; D016202:N-Methylaspartate; C012058:tenocyclidine; D008274:Magnesium; D010622:Phencyclidine; D000518:Eflornithine