Systemic administration of kainic acid differentially regulates the levels of prodynorphin and proenkephalin mRNA and peptides in the rat hippocampus.
The effects of systemic kainic acid (KA) administration on hippocampal levels of prodynorphin and proenkephalin mRNA, as well as opioid peptides derived from these precursors, were evaluated. A single subcutaneous injection of KA induced a range of seizure states, from mild wet dog shakes to generalized motor seizures. Northern blot analysis of hippocampal mRNA revealed an increase in both prodynorphin and proenkephalin mRNA levels which corresponded to the intensity of the convulsions. Conversely, hippocampal levels of immunoreactive dynorphin A (1-8) and [Met]5-enkephalin were decreased as a function of seizure frequency and intensity. The time course of KA-induced alterations in prodynorphin and proenkephalin mRNA and peptide levels was also investigated. Hippocampal prodynorphin mRNA levels rose at a dramatic rate. At 3 h following KA administration, mRNA levels were maximally elevated approximately 13-fold. The levels decreased over a 48 h period, eventually reaching control values. In contrast, proenkephalin mRNA levels increased more slowly. At 24 h, a maximal 24-fold increase was observed. At 72 h after injection, proenkephalin mRNA levels were still slightly elevated. In the same experiment, immunoreactive enkephalin peptide levels, although somewhat decreased at 3-12 h, began to increase between 12 and 24 h after injection, and were still rising at 72 h. In marked contrast, immunoreactive dynorphin peptide levels ranged from 40% to 80% of control values at all times tested.(ABSTRACT TRUNCATED AT 250 WORDS)
Douglass
J
J
Vollum Institute, Oregon Health Sciences University, Portland 97201.
Grimes
L
L
Shook
J
J
Lee
P H
PH
Hong
J S
JS
D000591:Amino Acid Isomerases / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D004723:Endorphins / Q000096:biosynthesis / Q000378:metabolism; D004745:Enkephalins / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007279:Injections, Subcutaneous; D007608:Kainic Acid / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D008297:Male; D019696:Peptidylprolyl Isomerase; D011498:Protein Precursors / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D011916:Rats, Inbred F344; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism
D002352:Carrier Proteins; D004723:Endorphins; D004745:Enkephalins; D011498:Protein Precursors; D012333:RNA, Messenger; C029992:proenkephalin; C033660:preproenkephalin; D000591:Amino Acid Isomerases; D019696:Peptidylprolyl Isomerase; D007608:Kainic Acid