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  • Title: Xylamine, an irreversible inhibitor of norepinephrine uptake, is transported by this same uptake mechanism in cultured rat superior cervical ganglia.
    Author: Fischer JB, Waggaman LA, Ransom RW, Cho AK.
    Journal: J Pharmacol Exp Ther; 1983 Sep; 226(3):650-5. PubMed ID: 6887005.
    Abstract:
    The accumulation of tritium-labeled xylamine ([3H]XYL), an irreversible inhibitor of neuronal norepinephrine (NE) uptake, was studied in organ-cultured rat superior cervical ganglia (SCG). At concentrations below those which significantly inhibit NE uptake, [3H]XYL accumulation was linear with time for up to 2 hr; at higher concentrations, accumulation slowed within the first 10 min. [3H]XYL accumulation was inhibited by desipramine, cocaine, bretylium and by NE at concentrations similar to those required to inhibit NE uptake. Replacing Na+ with Li+ in the bathing medium also inhibited [3H]XYL accumulation by about 70%. After 2 days of organ culture, SCG [3H]XYL accumulation was increased in parallel with an increase in NE uptake. Reserpine pretreatment of SCG did not affect [3H]XYL accumulation. The hydrolysis product of XYL, xylaminol, was also accumulated by SCG, but its accumulation was not inhibited by desipramine or the absence at Na+. By using trichloroacetic acid precipitation followed by ethanol extractions, about 40% of the accumulated tritium appeared to be irreversibly bound to protein, whereas about 30% appeared to be bound to lipids. We conclude that XYL is accumulated in sympathetic neurons by the NE uptake system and that this accumulation may be necessary in order for XYL to produce its irreversible inhibition of NE uptake.
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