The effects of xylamine, a nitrogen mustard on [3H]norepinephrine accumulation in rabbit aorta.

Xylamine (N-2-chloroethyl-N-ethyl-2-methylbenzylamine) irreversibly inhibits [3H]norepinephrine accumulation by rabbit aortic rings in vitro. Inhibition is observed when aortic rings are exposed to xylamine, washed and [3H]norepinephrine accumulation is measured in media free of xylamine. This dose-dependent effect, with an I50 of 10(-7) M, is prevented by coincubation of xylamine with the reversible uptake inhibitors cocaine and amphetamine in the incubation bath during exposure of the tissue to xylamine. The action of xylamine is also sodium dependent, since when tissue was exposed to xylamine in sodium-free Krebs' solution, xylamine had no action. Reduction of potassium ion concentration and the presence of ouabain also protected against xylamine inhibition. These results indicate that xylamine action involves interaction with the neuronal uptake system in a manner very similar to norepinephrine.