The accumulation and metabolism of (-)-noradrenaline by cells in culture.

1. Cultured bovine embryonic tracheal cells, EbTr (NBL-4) possess a process for the intracellular accumulation of (-)-noradrenaline with the characteristics generally ascribed to extraneuronal uptake by cardiac and smooth muscle cells in the body. It has a K(m) of 2.6 x 10(-4)M.2. The accumulation process is inhibited competitively by normetanephrine, but only at relatively high concentrations, IC50=2.1 x 10(-4)M. Inhibition also occurs with 17-beta-oestradiol, IC50=1.3 x 10(-5)M.3. The noradrenaline metabolites, 3,4-dihydroxy-mandelic acid and 3,4-dihydroxy-phenylglycol potentiate accumulation and reduce intracellular levels of normetanephrine in a similar manner to known inhibitors of catechol-O-methyl transferase.4. It is suggested that intracellular, rather than extracellular, normetanephrine may exert feedback inhibition upon noradrenaline accumulation by combining with the transport process at the inner surface of the cell membrane.