TY - JOUR
T1 - Excitatory amino acid regulation of the enkephalin phenotype in mouse embryonic spinal cord cultures
AU - Summers, Robert W.
AU - Wu, Xi Ru
AU - Fitzgerald, Sandra C.
AU - Brenneman, Douglas E.
AU - Agoston, Denes v.
PY - 1993/6/8
Y1 - 1993/6/8
N2 - Expression of the preproenkephalin gene in developing spinal cord-dorsal root ganglia (SC-DRG) cultures was determined by Northern analysis following treatments with different agonists and antagonists of the glutamate receptor. Cultures (10-12 days old) were treated with various concentrations (10-7-10-3 M) of N-methyl-d-aspartate (NMDA), quisqualate, kainic acid (KA), 2-amino-5-phosphonovaleric acid (APV) and 5-methyl-10,11-dihydro-5H-dibenzo[a, d]cyclohepten-5,10-imine maleate (MK801) either with or without blocking spontaneous electrical activity with 1 μM tetrodotoxin (TTX). In electrically active cultures, treatments with NMDA and KA increased preproenkephalin transcripts (mRNAppENK), showing maximum effects at 1 μM (4-fold and 2-fold, respectively), while treatments with quisqualate and MK801 caused concentration-dependent down-regulation in mRNAppENK. The most effective concentrations of NMDA (1 μM) and quisqualate (10 μM) altered mRNAppENK levels within 4 h of treatment and peaked after 24 h for NMDA and 48 h for quisqualate treatment. Co-treatment with APV completely blocked the NMDA-induced rise of mRNAppENK. During electrical blockade, none of the concentrations of NMDA tested showed any effect on enkephalin expression, neither could NMDA pre-treatment prevent the TTX-induced down-regulation of mRNAppENK. Our results indicate that the activity-dependent establishment of the enkephalin phenotype is modulated through the selective activation of the NMDA-glutamate receptor.
AB - Expression of the preproenkephalin gene in developing spinal cord-dorsal root ganglia (SC-DRG) cultures was determined by Northern analysis following treatments with different agonists and antagonists of the glutamate receptor. Cultures (10-12 days old) were treated with various concentrations (10-7-10-3 M) of N-methyl-d-aspartate (NMDA), quisqualate, kainic acid (KA), 2-amino-5-phosphonovaleric acid (APV) and 5-methyl-10,11-dihydro-5H-dibenzo[a, d]cyclohepten-5,10-imine maleate (MK801) either with or without blocking spontaneous electrical activity with 1 μM tetrodotoxin (TTX). In electrically active cultures, treatments with NMDA and KA increased preproenkephalin transcripts (mRNAppENK), showing maximum effects at 1 μM (4-fold and 2-fold, respectively), while treatments with quisqualate and MK801 caused concentration-dependent down-regulation in mRNAppENK. The most effective concentrations of NMDA (1 μM) and quisqualate (10 μM) altered mRNAppENK levels within 4 h of treatment and peaked after 24 h for NMDA and 48 h for quisqualate treatment. Co-treatment with APV completely blocked the NMDA-induced rise of mRNAppENK. During electrical blockade, none of the concentrations of NMDA tested showed any effect on enkephalin expression, neither could NMDA pre-treatment prevent the TTX-induced down-regulation of mRNAppENK. Our results indicate that the activity-dependent establishment of the enkephalin phenotype is modulated through the selective activation of the NMDA-glutamate receptor.
KW - Central nervous system
KW - Development
KW - Enkephalin
KW - N-Methyl-d-aspartate
KW - Phenotype
UR - http://www.scopus.com/inward/record.url?scp=0027255810&partnerID=8YFLogxK
U2 - 10.1016/0165-3806(93)90137-Y
DO - 10.1016/0165-3806(93)90137-Y
M3 - Article
C2 - 8353931
AN - SCOPUS:0027255810
SN - 0165-3806
VL - 73
SP - 185
EP - 192
JO - Developmental Brain Research
JF - Developmental Brain Research
IS - 2
ER -