Polyamines modulate events mediated by the N-methyl-D-aspartate (NMDA) receptor complex through an ifenprodil-insensitive pathway: in vivo measurements of cyclic GMP in the cerebellum.
In the present investigation, the effects of polyamines, spermidine and spermine on events mediated by the N-methyl-D-aspartate (NMDA) receptor complex were examined. Spermine and spermidine did not alter basal levels of cyclic GMP (cGMP) in the cerebellum of the mouse, over a wide range of concentrations. However, exogenously added spermine, spermidine, D- and L-ornithine and putrescine attenuated the increases in cGMP seen after the administration of D-serine, an agonist of the NMDA receptor-associated glycine recognition sites. Spermine and/or spermidine also antagonized harmaline-, methamphetamine- and pentylenetetrazol-induced increases in the levels of cGMP. Spermidine also potentiated (+)-MK-801 (dizocilipine)-induced attenuation of basal levels of cGMP. Intracerebroventricular administration of ifenprodil, a suggested polyamine antagonist, did not antagonize spermine- and spermidine-induced attenuation of the response to D-serine. These data suggest that exogenously added polyamines attenuate events mediated by the NMDA receptor complex, in an ifenprodil-insensitive manner.
Rao
T S
TS
CNS Diseases Research Division, Searle Research and Development, G.D. Searle & Co., St Louis, MO 63198.
Cler
J A
JA
Mick
S J
SJ
Iyengar
S
S
Wood
P L
PL
D000818:Animals; D015317:Biogenic Polyamines / Q000494:pharmacology*; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology; D051379:Mice; D009434:Neural Pathways / Q000187:drug effects; D009952:Ornithine / Q000494:pharmacology; D010433:Pentylenetetrazole / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D011700:Putrescine / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D013095:Spermidine / Q000494:pharmacology; D013096:Spermine / Q000494:pharmacology
D015317:Biogenic Polyamines; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D013096:Spermine; D008694:Methamphetamine; D016291:Dizocilpine Maleate; D009952:Ornithine; D006152:Cyclic GMP; C010739:ifenprodil; D013095:Spermidine; D011700:Putrescine; D010433:Pentylenetetrazole