RT Journal Article
SR Electronic
T1 Use of mRNA hybridization and radioimmunoassay to study mechanisms of drug-induced accumulation of enkephalins in rat brain structures.
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 86
OP 91
VO 28
IS 1
A1 I Mocchetti
A1 J P Schwartz
A1 E Costa
YR 1985
UL http://molpharm.aspetjournals.org/content/28/1/86.abstract
AB The repeated administration of haloperidol or fenfluramine for several days led to an increase of enkephalin content in specific brain areas. In order to characterize the nature of the dynamic changes underlying this increase, we measured the content of proenkephalin mRNA (PE-mRNA), of high molecular weight (HMW) enkephalin precursors, and of low molecular weight enkephalin peptides (LMW) in various brain areas. To measure PE-mRNA, we hybridized the specific mRNA with a [32P]cDNA probe for human pheochromocytoma PE. HMW and LMW enkephalin content was measured by radioimmunoassay after separation of the immunoreactive peaks by Bio-Gel P-2 column chromatography and enzymatic digestion of the precursors. Haloperidol treatment increased enkephalins, the precursor, and PE-mRNA content in the striatum, suggesting that this drug might increase enkephalin steady state by increasing transcription, translation, or both processes. In contrast, fenfluramine increased hypothalamic and striatal enkephalin content by preferentially reducing neuropeptide utilization or decreasing its catabolism without changing its synthesis.