Effects of N6-Methyladenosine on the Synthesis of Phenylethanolamine N-Methyltransferase in Cultured Explants of Rat Adrenal Medulla

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Abstract
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-methyltransferae (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 oxidae (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.