Metabolic fate of 3H-noradrenaline released from the mouse hypothalamus

In slices of mouse hypothalamus labelled in vitro with 3H-noradrenaline (3-H-NA), the deaminated metabolite 3H-3,4-dihydroxyphenylglycol (3H-DOPEG), represented 40.2 +/- 2.6% of the total outflow of radioactivity and was the main fraction in the spontaneous efflux. Inhibition of neuronal monoamine oxidase by exposure to 60 micron bretylium, reduced the outflow of 3H-DOPEG to 9.7 +/0 0.3%. At the same time, the proportion of 3H-normetanephrine (3H-NMN) was significantly increased. On the other hand, an increased outflow of 3H-DOPEG and a lower proportion of 3H-NMN was obtained in the presence of 2.9 micron of the reserpine like agent Ro 4-1284. It is suggested that in the mouse hypothalamus, the deaminated metabolite, DOPEG, is formed inside the nerve terminals, while the O-methylated metabolite, NMN, might result from the activity of extraneuronal catechol O-methyltransferase.