Relationship between the regulation of enkephalin-containing peptide and dopamine beta-hydroxylase levels in cultured adrenal chromaffin cells.
Adrenal medullary chromaffin cells were maintained under conditions known to increase their cellular levels of enkephalin-containing peptides and the effects of these treatments on another chromaffin vesicle component, dopamine beta-hydroxylase, were examined. Catecholamine-depleting drugs, such as tetrabenazine, and cyclic nucleotide-elevating drugs, including forskolin, 8-bromo-cyclic AMP, and theophylline, increase chromaffin cell enkephalin-containing peptide levels but fail to increase dopamine beta-hydroxylase. In contrast, insulin treatment increases the levels of both enkephalin-containing peptides and dopamine beta-hydroxylase. The increased amounts of enkephalin-containing peptides produced by tetrabenazine and by insulin are stored in subcellular particles with properties identical to chromaffin vesicles on density-gradient centrifugation. These results suggest that following insulin treatment chromaffin cells synthesize new chromaffin vesicles with a full complement of enkephalin-containing peptides, but that after treatment with catecholamine-depleting or cyclic nucleotide-related agents enkephalin-containing peptides can be inserted into preexisting vesicles or that new vesicles, made as a part of the normal turnover of cellular components, contain elevated peptide levels.
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000313:Adrenal Medulla / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D002458:Cell Fractionation; D002478:Cells, Cultured; D002837:Chromaffin Granules / Q000187:drug effects / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism*; D004745:Enkephalins / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D010455:Peptides / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D013747:Tetrabenazine / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology
D004745:Enkephalins; D007328:Insulin; D010455:Peptides; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D013806:Theophylline; D004299:Dopamine beta-Hydroxylase; D013747:Tetrabenazine