Permissive effect of dexamethasone on the increase of proenkephalin mRNA induced by depolarization of chromaffin cells.
In cultured bovine chromaffin cells, changes in the dynamic state of enkephalin stores elicited experimentally were studied by measuring cellular proenkephalin mRNA, as well as enkephalin precursors and authentic enkephalin content of cells and culture media. In parallel, tyrosine hydroxylase mRNA and catecholamine cell content were also determined. Low concentrations (0.5-100 pM) of dexamethasone increased the cell contents of proenkephalin mRNA and enkephalin-containing peptides. High concentrations of the hormone (1 microM) were required to increase the cell contents of tyrosine hydroxylase mRNA and catecholamines. Depolarization of the cells with 10 microM veratridine resulted in a depletion of enkephalin and catecholamine stores after 24 hr. The enkephalin, but not the catecholamine, content was restored by 48 hr. An increase in proenkephalin mRNA content might account for the recovery; this increase was curtailed by tetrodotoxin and enhanced by 10 pM dexamethasone. Tyrosine hydroxylase mRNA content was not significantly modified by depolarization, even in the presence of 1 microM dexamethasone. Aldosterone, progesterone, testosterone, or estradiol (1 microM) failed to change proenkephalin mRNA. Hence, dexamethasone appears to exert a specific permissive action on the stimulation of the proenkephalin gene elicited by depolarization. Though the catecholamines and enkephalins are localized in the same chromaffin granules and are coreleased by depolarization, the genes coding for the processes that are rate limiting in the production of these neuromodulators can be differentially regulated.
Naranjo
J R
JR
Mocchetti
I
I
Schwartz
J P
JP
Costa
E
E
D000313:Adrenal Medulla / Q000166:cytology / Q000502:physiology*; D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D004745:Enkephalins / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D008564:Membrane Potentials; D011498:Protein Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics; D014701:Veratridine / Q000494:pharmacology
D002395:Catecholamines; D004745:Enkephalins; D011498:Protein Precursors; D012333:RNA, Messenger; C029992:proenkephalin; D013779:Tetrodotoxin; D014701:Veratridine; D003907:Dexamethasone; D014446:Tyrosine 3-Monooxygenase