Effects of N6-methyladenosine on the synthesis of phenylethanolamine N-methyltransferase in cultured explants of rat adrenal medulla.

Explants of adrenal medullae were cultured in defined media for up to 48 h, during which time the tissue remained histologically intact. Addition of N6-methyladenosine to the medium led to a diminution in the activity of phenylethanolamine N-methyltransferase (EC 2.1.1.28) in the tissue. The enzyme activity was inversely proportional to the concentration N6-methyladenosine in the culture medium. The extent of loss of phenylethanolamine N-methyltransferase, as measured by immunochemical titration, corresponded to the degree of loss in enzyme activity under the same conditions. Furthermore, the decreased amount of enzyme protein was due to a decrease in the rate of synthesis of phenylethanolamine N-methyltransferase. Neither adenosine nor several methylated nucleosides, including 7-methylguanosine, N2-methylguanosine, and 5-methylcytosine, had an effect on the enzyme. Two other adrenal medullary enzymes, monoamine oxidase (EC 1.4.3.4) and acid phosphatase (EC 3.1.3.2), were not affected by addition of N6-methyladenosine to the medium. The results are consistent with the view that this effect of N6-methyladenosine on the concentration of phenylethanolamine N-methyltransferase is due to an inhibition of its biosynthesis rather than to an alteration of its rate of degradation.