Js. Won et al., THE MODULATORY ROLE OF NITRIC-OXIDE IN THE REGULATION OF PROENKEPHALIN AND PRODYNORPHIN GENE EXPRESSIONS INDUCED BY KAINIC ACID IN RAT HIPPOCAMPUS, Molecular brain research, 56(1-2), 1998, pp. 76-83
The effect of L-arginine (L-ARG), a nitric oxide donor, or N-omega-nit
ro-L-arginine (L-NAME), a nitric oxide synthase inhibitor, on the regu
lation of kainic acid(KA)-induced proenkephalin (proENK) and prodynorp
hin (proDYN) mRNA expressions in rat hippocampus was studied. The proE
NK and proDYN mRNA levels were markedly increased 6 h after KA (10 mg/
kg, i.p.) administration. The elevations of both proENK and proDYN mRN
A 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 wit
h L-NAME (200 mg/kg, i.p.). The blockade of KA-induced proENK and proD
YN mRNA levels by the pre-treatment with L-ARG was well correlated wit
h proto-oncoprotein levels, such as c-Fos, Fra-2, FosB, JunD, JunB, an
d 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-fo
s mRNA levels in addition to their protein product levels, although th
e pre-treatment with L-NAME did not affect KA-induced FosB, Fra-2, Jun
B, and JunD protein levels at 6 h after treatment. In addition, the pr
e-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 expr
ession, and its inhibitory action may be mediated through reducing the
proto-oncoprotein levels, such as c-Fos, Fra-2, FosB, c-Jun, JunD, an
d JunB. In addition, L-NAME potentiated the c-Fos or c-Jun gene expres
sion, as well as AP-1 or ENKCRE-2 DNA binding activity. However, these
increases did not show the potentiative effect on KA-induced increase
s of proENK and proDYN mRNA level. (C) 1998 Elsevier Science B.V.