The modulatory role of nitric oxide in the regulation of proenkephalin and prodynorphin gene expressions induced by kainic acid in rat hippocampus.
The effect of L-arginine (L-ARG), a nitric oxide donor, or Nomega-nitro-L-arginine (L-NAME), a nitric oxide synthase inhibitor, on the regulation of kainic acid (KA)-induced proenkephalin (proENK) and prodynorphin (proDYN) mRNA expressions in rat hippocampus was studied. The proENK and proDYN mRNA levels were markedly increased 6 h after KA (10 mg/kg, i.p.) administration. The elevations of both proENK and proDYN mRNA levels induced by KA was effectively inhibited by pre-administration of L-ARG (400 mg/kg, i.p.), but was not affected by pre-treatment with L-NAME (200 mg/kg, i.p.). The blockade of KA-induced proENK and proDYN mRNA levels by the pre-treatment with L-ARG was well correlated with proto-oncoprotein levels, such as c-Fos, Fra-2, FosB, JunD, JunB, and c-Jun, as well as AP-1 and ENKCRE-2 DNA binding activities. The pre-administration with L-NAME further increased KA-induced c-jun and c-fos mRNA levels in addition to their protein product levels, although the pre-treatment with L-NAME did not affect KA-induced FosB, Fra-2, JunB, and JunD protein levels at 6 h after treatment. In addition, the pre-administration with L-NAME further increased the KA-induced AP-1 and ENKCRE-2 DNA binding activities. Our results suggest that L-ARG plays an important role in inhibiting KA-induced proENK or proDYN mRNA expression, and its inhibitory action may be mediated through reducing the proto-oncoprotein levels, such as c-Fos, Fra-2, FosB, c-Jun, JunD, and JunB. In addition, L-NAME potentiated the c-Fos or c-Jun gene expression, as well as AP-1 or ENKCRE-2 DNA binding activity. However, these increases did not show the potentiative effect on KA-induced increases of proENK and proDYN mRNA level.
Won
J S
JS
Department of Pharmacology, Institute of Natural Medicine, College of Medicine, Hallym University, 1 Okchun-Dong, Chunchon, Kangwon-Do, 200-702, South Korea.
Im
Y B
YB
Kim
Y H
YH
Song
D K
DK
Huh
S O
SO
Suh
H W
HW
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism; D004745:Enkephalins / Q000096:biosynthesis*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D011498:Protein Precursors / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018808:Transcription Factor AP-1 / Q000378:metabolism
D004268:DNA-Binding Proteins; D004745:Enkephalins; D011498:Protein Precursors; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; C029992:proenkephalin; D009569:Nitric Oxide; C033660:preproenkephalin; D001120:Arginine; D007608:Kainic Acid; D019331:NG-Nitroarginine Methyl Ester