Acute down-regulation of oxytocin and vasopressin mRNA levels following metrazole-induced seizure in the rat.
Following our recent demonstration of metrazole-induced immediate-early gene expression in the hypothalamic supraoptic nucleus (SON), we have now performed a mRNA and transcription analysis to determine the consequences of metrazole treatment for neurohypophyseal peptide gene expression in male rats. Levels of hypothalamic vasopressin (VP) and oxytocin (OT) mRNA were significantly reduced at 2 and 4 h after metrazole (50 mg/kg, i.p.), whereas pro-dynorphin mRNA was significantly elevated at 2 h. No changes in mRNA levels were found at 8, 24 or 48 h after treatment. Another convulsant (kainic acid, 8 mg/kg, i.p.) elicited similar effects on VP and OT mRNAs at 2 h. Specific analysis of the SON, following metrazole, revealed an equivalent effect on VP and OT mRNA levels but a nuclear run-on assay did not detect any change in SON VP gene transcription at 0.5, 1 and 2 h after treatment. The results provide evidence of a novel mechanism which may provide an additional level of control in the regulation of neuropeptide gene expression.
Carter
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DA
Neuropeptide Laboratory, National University of Singapore.
Murphy
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D000818:Animals; D015152:Blotting, Northern; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D004745:Enkephalins / Q000096:biosynthesis; D015870:Gene Expression / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010121:Oxytocin / Q000096:biosynthesis*; D010433:Pentylenetetrazole / Q000633:toxicity*; D010904:Pituitary Gland, Posterior / Q000187:drug effects / Q000378:metabolism; D011498:Protein Precursors / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*; D013495:Supraoptic Nucleus / Q000187:drug effects / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014667:Vasopressins / Q000096:biosynthesis*
D004745:Enkephalins; D011498:Protein Precursors; D012333:RNA, Messenger; D014667:Vasopressins; D010121:Oxytocin; C033660:preproenkephalin; D010433:Pentylenetetrazole