Wan D C, Marley P D, Livett B G
Department of Biochemistry, University of Melbourne, Parkville, Vic., Australia.
Brain Res Mol Brain Res. 1991 Jan;9(1-2):135-42. doi: 10.1016/0169-328x(91)90138-n.
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.
在牛肾上腺嗜铬细胞培养物中,研究了前脑啡肽原A(ProEnk A)mRNA和苯乙醇胺N-甲基转移酶(PNMT)mRNA对环磷酸腺苷类似物、福斯高林和佛波酯的反应。嗜铬细胞暴露于1 mM二丁酰环磷酸腺苷24小时后,ProEnk A mRNA水平显著升高,而对PNMT mRNA水平无显著影响。暴露于促肿瘤佛波酯(佛波醇12-肉豆蔻酸酯13-乙酸酯、佛波醇12,13-二丁酸酯或4-β-佛波醇12,13-二癸酸酯)12小时的细胞对PNMT mRNA和ProEnk A mRNA表达有不同程度的激活作用。低浓度(10^(-9)至10^(-8)M)的这些佛波酯可显著提高PNMT mRNA水平,但在较高浓度(10^(-...)