Kainic acid alters the metabolism of Met5-enkephalin and the level of dynorphin A in the rat hippocampus.
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.
D000818:Animals; D004399:Dynorphins / Q000378:metabolism*; D004744:Enkephalin, Methionine / Q000378:metabolism*; D004745:Enkephalins / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism*; D006651:Histocytochemistry; D007120:Immunochemistry; D007608:Kainic Acid / Q000494:pharmacology*; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D011916:Rats, Inbred F344; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology
D004745:Enkephalins; D011498:Protein Precursors; D012333:RNA, Messenger; D004744:Enkephalin, Methionine; D004399:Dynorphins; C033660:preproenkephalin; D007608:Kainic Acid