Coordinate and differential regulation of proenkephalin A and PNMT mRNA expression in cultured bovine adrenal chromaffin cells: responses to cAMP elevation and phorbol esters.

The expression of proenkephalin A (ProEnk A) mRNA and phenylethanolamine N-methyltransferase (PNMT) mRNA in response to cAMP analogues, forskolin and phorbol esters was examined in cultures of bovine adrenal chromaffin cells. Exposure of chromaffin cells to 1 mM dibutyryl cAMP for 24 h increased significantly the levels of ProEnk A mRNA, with no significant effect on the levels of PNMT mRNA. Cells exposed to the tumor promoting phorbol esters (phorbol 12-myristate 13-acetate, phorbol 12,13-dibutyrate or 4-beta-phorbol 12,13-didecanoate) for 12 h differentially activated PNMT mRNA and ProEnk A mRNA expression. The levels of PNMT mRNA were dramatically elevated in response to low concentrations (10(-9) to 10(-8)M) of these phorbol esters, but these increases were diminished at higher concentrations (10(-7) to 10(-6) M) of the phorbol esters. These responses were synergistically potentiated by dexamethasone (1 microM), a synthetic glucocorticoid. None of these effects was seen with the biologically inactive phorbol ester, 4-alpha-phorbol 12,13-didecanoate. By contrast, the expression of ProEnk A mRNA was activated by the tumor promoting phorbol esters in a concentration-dependent manner. The results of this study demonstrate a differential stimulatory effect of second messenger mechanisms in the control of PNMT and ProEnK A mRNA expression and provide further evidence for an independent control for the enkephalin and adrenaline synthesis in these cells.