Actions of D-cycloserine at the N-methyl-D-aspartate-associated glycine receptor site in vivo.
The antibiotic, D-cycloserine has been shown to be a partial agonist at the N-methyl-D-aspartate (NMDA)-coupled, strychnine-insensitive glycine receptor by in vitro receptor binding. This partial agonism was further investigated in an in vivo system, by monitoring changes in levels of cyclic guanosine-monophosphate (cGMP), a well characterized second messenger response, mediated by the NMDA receptor complex, in the cerebellum of the mouse. Parenteral injections of D-cycloserine produced a biphasic dose-response curve which suggested partial agonism. In support of this contention, when intracerebellar injections were made together with D-serine, a glycine agonist, D-cycloserine attenuated the N-methyl-D-aspartate receptor-mediated increase in levels of cGMP. Likewise, systemic administration of D-cycloserine attenuated increases in cGMP induced by pentylenetetrazol. These data are relevant to the study of N-methyl-D-aspartate-mediated neurotransmission, since D-cycloserine is a parenterally bioavailable compound, with both agonist and depressant properties at the N-methyl-D-aspartate-associated glycine receptor.
Emmett
M R
MR
Searle Research and Development, Monsanto Company, St Louis, MO 63198.
Mick
S J
SJ
Cler
J A
JA
Rao
T S
TS
Iyengar
S
S
Wood
P L
PL
D000818:Animals; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D003523:Cycloserine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005998:Glycine; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D017981:Receptors, Neurotransmitter / Q000187:drug effects*
D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D003523:Cycloserine; D006152:Cyclic GMP; D005998:Glycine