Brief cortisol exposure elevates adrenal phenylethanolamine N-methyltransferase after a necessary lag period

Abstract

The present study, using bovine adrenal medullary cells, characterized in detail the time course of regulation of phenylethanolamine N-methyltransferase activity following brief glucocorticoid exposure. Cortisol pulses (10(-4) and 10(-5) M), as short as 15 min, increased phenylethanolamine N-methyltransferase activity measured 2 days following cortisol exposure, with a required lag period of 18 h or more. Phenylethanolamine N-methyltransferase activity was increased 2 days following brief (2 h) exposure to cortisol in concentrations that reach the medulla in vivo (10(-6) to 10(-4) M). Phenylethanolamine N-methyltransferase activity following both continuous and 2 h pulses of 10(-5) M cortisol were reduced by the glucocorticoid receptor antagonist, RU 38486. A 2 h pulse of nicotine (10(-5) M) increased phenylethanolamine N-methyltransferase activity with a lag period of at least 18 h, while combination treatment of nicotine and cortisol (10(-4) M) produced significantly higher increases in phenylethanolamine N-methyltransferase compared to either treatment alone. Therefore, this study provides novel in vitro evidence for the regulation of adrenomedullary phenylethanolamine N-methyltransferase activity, following a necessary lag period, by acute changes in both cortisol and nicotine.