Accumulation of3H-(?)noradrenaline in the rabbit aorta not related to uptake1 and uptake2, but sensitive to 3,4-dihydroxy-2-methylpropiophenone (U-0521) and oxytetracycline

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Abstract
Some of the extraneuronal accumulation of3H-(−)noradrenaline in the rabbit aorta was resistant to uptake2 inhibitors (corticosterone, normetanephrine, phenoxybenzamine). Even combined treatment of the tissue with the competitive inhibitor corticosterone (87 μmol·l−1) and the irreversible inhibitor phenoxybenzamine (90 μmol·l−1) was not more effective than was corticosterone alone. The corticosterone-resistant extraneuronal accumulation of3H-(−)noradrenaline (0.12 μmol·l−1) was reduced by about 30% by the COMT inhibitor U-0521 (1000 μmol·l−1) and by oxytetracycline (100 μmol·l−1). Combined treatment with U-0521 and oxytetracycline was not more effective than was U-0521 alone. Already 1 μmol·l−1 U-0521 had a half-maximal effect, i.e., it reduced accumulation by 15%. This effect of U-0521 was not related to its known ability to block uptake2. The catechol U-0521 probably inhibited binding of noradrenaline to a catechol-specific site. Furthermore, the accumulation was sensitive to the two iron-chelating agents deferoxamine and phenanthroline but not to ascorbic acid and N-ethylamaleimide. A relatively high formation of 3,4-dihydroxymandelic acid (DOMA) took place in the corticosterone-resistant extraneuronal compartment of the mechanically denervated aorta. This formation of DOMA was probably a consequence of tissue injury brought about by removing the adventitia.