Inactivation of norepinephrine in an isolated vein.

Canine isolated vein strips were labeled with tritiated norepinephrine (NE). Tritiated NE and its metabolites appearing during spontaneous outflow and during electric stimulation (10 Hz, 100 V, 2 msec, 5 minutes) were determined. The spontaneous outflow of tritiated compounds from the vein contained 90.5% metabolic products of NE, chiefly, the O-methylated and deaminated products (OMDA) and 3,4-dihydroxyphenylglycol (DOPEG). During electric stimulation we observed approximately a 3-fold increase in the outflow of radioactivity, consisting of 39% NE, 25% OMDA and 19% DOPEG. Normetanephrine (NMN) and 3,4-dihydroxymandelic acid represented only 10 and 6%, respectively. Blockade of reuptake of NE into nerve terminals by cocaine did not prevent the appearance of deaminated metabolites in the spontaneous outflow. However, when the vein was electrically stimulated the increase of DOPEG was alomst completely blocked. Blockade of extraneuronal uptake of NE by desoxycorticosterone did not modify significantly the composition of spontaneous outflow. However, desoxycorticosterone caused a marked decrease of NMN and OMDA during electric stimulation. The inhibition of catechol-O-methyltransferase by U-0521 caused a decrease of NMN and OMDA during the spontaneous outflow, and a shift from O-methylation to deamination of NE. During electric stimulation, U-0521 markedly decreased the formation of NMN and OMDA and caused an increase in outflow of NE.