Negative feedback regulation of the content of proenkephalin mRNA in chromaffin cell cultures.
The content of proenkephalin messenger RNA (PEmRNA) in cultured bovine adrenal chromaffin cells was reduced in the presence of reserpine (1 nM to 0.1 microM) with a return to basal levels 3 days after removal of the drug. In these cells, the basal release of Met5-enkephalin-Arg6-Phe7 immunoreactivity (MERF-IR) into the medium was significantly decreased when the cultures were pretreated with 0.2 microM reserpine for 3 days. The addition of 0.1 microM etorphine for 3 days also decreased the basal release of MERF-IR without depleting stores of catecholamines. Neither drug modified the total (cells + medium) amount of MERF-IR. In contrast, reserpine was without effect on levels of PEmRNA or release of Met5-enkephalin immunoreactivity (ME-IR) in primary cultures of the striatum of the fetal rat. The present data establish a correlation between inhibition of the secretion of enkephalin and reduced accumulation of its specific mRNA, suggesting a negative feedback inhibition by low molecular weight enkephalins.
Fidia-Georgetown Institute for the Neurosciences, Georgetown University Medical School, Washington, DC 20007.
J R
JR
Naranjo
B C
BC
Wise
B
B
Mellstrom
E
E
Costa
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D002838:Chromaffin System / Q000166:cytology; D004745:Enkephalins / Q000235:genetics*; D004837:Epinephrine / Q000032:analysis; D005246:Feedback; D007120:Immunochemistry; D009638:Norepinephrine / Q000032:analysis; D010455:Peptides / Q000032:analysis; D011498:Protein Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis*; D012110:Reserpine / Q000494:pharmacology
D004745:Enkephalins; D010455:Peptides; D011498:Protein Precursors; D012333:RNA, Messenger; C029992:proenkephalin; D012110:Reserpine; D009638:Norepinephrine; D004837:Epinephrine