THE RELATIONSHIP BETWEEN RADIOACTIVITY AND NOREPINEPHRINE CONCENTRATIONS IN THE BRAINS AND HEARTS OF MICE FOLLOWING ADMINISTRATION OF LABELED METHYLDOPA OR 6-HYDROXYDOPAMINE

¹ Merck Institute for Therapeutic Research, West Point, Pennsylvania

After the administration of 2-C¹⁴-methyldopa to mice, both the brains and the hearts contained radioactivity which disappeared with time, but not completely until tissue norepinephrine concentrations had returned to essentially normal values. Extracts of the tissues contained a radioactive substance which on paper traveled with the same R_f as -methylnorepinephrine. Brain extracts contained, in addition, radioactivity which traveled with the R_f of methyldopa or methyldopamine, and which was an amine as shown by ion exchange chromatography. Reserpine (10 mg/kg) had no effect upon radioactivity in brain; however, it removed about 60% of the radioactivity in the heart. The ED5O of reserpine in depleting time heart of the labile radioactivity was about 10 times as large as its ED5O in depleting the heart of norepinephrine. It is concluded that -methylnorepinephrine, formed in the metabolism of administered methyldopa, displaced norepinephrine molecule for molecule, and that, conversely, with time norepinephrine displaced -methylnorepinephrine in the same way.

The administration of 2-C¹⁴-6-hydroxydopamine was followed by an accumulation of radioactivity in the heart which was reciprocally related to heart norepinephrine over the entire course of the experiment (44 days). It seems probable that 6-hydroxydopamine, or a metabolite, displaced norepinephrine molecule for molecule.