Glycine, glycinamide and D-serine act as positive modulators of signal transduction at the N-methyl-D-aspartate (NMDA) receptor in vivo: differential effects on mouse cerebellar cyclic guanosine monophosphate levels.
Direct intracerebellar (icb) administration of glycine, glycinamide and D-serine produced time- and dose-dependent changes in mouse cerebellar cGMP levels, indicating a modulation of ongoing neuronal activity through the NMDA receptor complex. Intracerebroventricular administration of glycinamide also produced a time-dependent change in cGMP levels, indicating a central mechanism of action. The icb dose-response data indicated a unimolecular interaction for these compounds. D-serine-, glycine-, and glycinamide-mediated increases in cGMP levels were reversed by the competitive NMDA antagonist, CPP and the NMDA-associated glycine receptor antagonist, HA-966, indicating mediation via the NMDA receptor complex. Glycine and D-serine were less effective than glycinamide at increasing cerebellar cGMP levels. In contrast, L- and D-serinamide did not affect cGMP levels. These results indicate that glycine receptor is not saturated under physiological conditions and also suggest possible existence of multiple glycine pools.
Rao
T S
TS
G. D. Searle & Co. Monsanto Company, St. Louis, MO 63198.
Cler
J A
JA
Emmett
M R
MR
Mick
S J
SJ
Iyengar
S
S
Wood
P L
PL
D000818:Animals; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology; D006152:Cyclic GMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005998:Glycine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D007276:Injections, Intraventricular; D007536:Isomerism; D008297:Male; D051379:Mice; D010622:Phencyclidine / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*; D012694:Serine / Q000008:administration & dosage / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*
D011760:Pyrrolidinones; D016194:Receptors, N-Methyl-D-Aspartate; D012694:Serine; C018556:glycine amide; C001369:1-hydroxy-3-amino-2-pyrrolidone; D006152:Cyclic GMP; D010622:Phencyclidine; D005998:Glycine