Negative feedback regulation of the content of proenkephalin MRNA in chromaffin cell cultures

Abstract

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 μM) with a return to basal levels 3 days after removal of the drug. In these cells, the basal release of Met 5-enkephalin-Arg 6-Phe 7 immunoreactivity (MERF-IR) into the medium was significantly decreased when the cultures were pretreated with 0.2 μM reserpine for 3 days. The addition of 0.1 μM 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 Met 5-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.