Journal of Neuroscience, Vol 6, 3094-3102, Copyright © 1986 by Society for Neuroscience
Kainic acid alters the metabolism of Met5-enkephalin and the level of dynorphin A in the rat hippocampus
T Kanamatsu, J Obie, L Grimes, JF McGinty, K Yoshikawa, S Sabol and JS Hong
Male Fischer-344 rats were given a single intrastriatal injection of kainic
acid (KA; 1 microgram/rat), which caused recurrent motor seizures lasting
3-6 hr. During the convulsive period, native Met5- enkephalin-like (ME-LI)
and dynorphin A (1-8)-like (DYN-LI) immunoreactivities in hippocampus
decreased by 31 and 63%, respectively. By 24 hr after dosing, the
hippocampal opioid peptides had returned to control levels, and by 48 hr
ME-LI had increased 270% and DYN-LI 150%. Immunocytochemical analysis
revealed that ME-LI and Leu5-enkephalin-like (LE-LI) immunostaining in the
mossy fibers of dentate granule cells and the perforant-temporoammonic
pathway had decreased visibly by 6 hr and had increased markedly by 48 hr
following KA. A visible decrease in DYN-LI in mossy fiber axons within 6 hr
was followed by a substantial increase by 48 hr. To determine whether the
increases in hippocampal ME-LI reflected changes in ME biosynthesis, levels
of mRNA coding for preproenkephalin (mRNAenk) and cryptic ME-LI cleaved by
enzyme digestion from preproenkephalin were measured. Following the
convulsive period (6 hr), mRNAenk was 400% of control, and by 24 hr,
cryptic ME-LI was 300% of control. Increases in native and cryptic ME-LI
and in mRNAenk were also noted in entorhinal cortex, but not in
hypothalamus or uninjected striatum. Our data suggest that KA-induced
seizures cause an increase in ME release, followed by a compensatory
increase in ME biosynthesis in the hippocampus and entorhinal cortex.
