The uptake of noradrenaline by human red blood cells and ghosts
A study has been made of the transport of noradrenaline into human red cells and resealed ghosts. In cells uptake appeared to obey the kinetics of simple diffusion, whilst in metabolically inert ghosts, uptake was identified as a low affinity high capacity saturable transport mechanism. Uptake was markedly temperature sensitive but not dependent upon cellular metabolism, consistent mth facilitated diffusion rather than active transport of noradrenaline. Non-competitive inhibition of uptake was achieved by a variety of structurally related compounds when present at either the inner or outer membrane surface. The ionic requirements for noradrenaline transport by red cells and ghosts have been examined. VJhen external sodium was replaced isosmotically by N-methyl-D-glucamine the apparent affinity for uptake by ghosts was modestly inhibited. Replacement of external sodium by potassium was ineffective, suggesting a requirement for both sodium and/or potassium. Specific sodium transport inhibitors were without effect and it was shown that the mechanism has no requirement for calcium or magnesium. Replacement of external chloride by either nitrate or methylsulphate stimulated red cell noradrenaline accumulation, but was ineffective in ghosts. It is suggested that anion substitution may act secondarily on transport by affecting binding and/or catecholamine metabolism. Noradrenaline uptake was inversely proportional to external hydrogen ion concentration, suggesting that lipophilic substrate is favoured for transport. It is concluded that noradrenaline transport does not occur via the "uptake 1" or "uptake 2" pathways characterised in other tissues. It has been shown that the slowly metabolised noradrenaline analogue, guanethidine, is accumulated by red cells. Guanethidine transport is saturable, sodium and chloride independent, and inhibition studies reveal separate routes of entry for this compound and noradrenaline. Noradrenaline has no effect upon red cell cation transport. Therefore, abnormalities reported in clinical disorders, such as essential hypertension, are not attributable to increased plasma noradrenaline concentration.