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

1. Some of the extraneuronal accumulation of 3H-(-)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 mumol . l-1) and the irreversible inhibitor phenoxybenzamine (90 mumol . l-1) was not more effective than was corticosterone alone. 2. The corticosterone-resistant extraneuronal accumulation of 3H-(-)noradrenaline (0.12 mumol . l-1) was reduced by about 30% by the COMT inhibitor U-0521 (1000 mumol . l-1) and by oxytetracycline (100 mumol . l-1). Combined treatment with U-0521 and oxytetracycline was not more effective than was U-0521 alone. Already 1 mumol . 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-ethylmaleimide. 3. 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.