caa a22 4500 469079363 CHVBK 20180323132945.0 cr unu---uuuuu 170328e19920401xx s 000 0 eng 10.1007/BF00176622 doi (NATIONALLICENCE)springer-10.1007/BF00176622 The force driving the extraneuronal transport mechanism for catecholamines (uptake2) [Elektronische Daten] [E. Schömig, J. Babin-Ebell, H. Russ, U. Trendelenburg] Summary: Recently, uptake2 was shown to exist in the clonal Caki-1 cell line. The aim of this study was two-fold: a) to determine, in Caki-1 cells, the intracellular fate of 3H-noradrenaline after its translocation by uptake2 and b) to analyse the force driving uptake2. Caki-1 cells have the characteristics of a "metabolizing system” in which the activity of catechol-O-methyl transferase (COMT) greatly exceeds that of monoamine oxidase (MAO). In all subsequent experiments these enzymes were inhibited. The determination of initial rates of uptake2 into Caki-I cells at an extracellular pH between 6.9 and 7.9 indicated that the protonated species of 3H-noradrenaline is transported. Depolarization of Caki-1 cells (by three different procedures) inhibited the inward transport. Determination of the time course of the specific accumulation of 3H-noradrenaline in Caki-I cells and of 3H-isoprenaline in the perfused rat heart (both mediated by uptake2) revealed that depolarization (by high K+) reduced the rate constant for inward transport (kIN) and increased that for outward movement (kOUT). Consequently, depolarization reduced the steady-state factor of accumulation. It is proposed that, as the protonated species of the substrates of uptake2 is transported, the membrane potential is likely to provide the driving force for uptake2. The fact that depolarization decreased kIN and increased kOUT agrees with this proposal, as do the magnitudes of the steady-state accumulation factors determined in Caki-I cells and perfused rat heart. Springer-Verlag, 1992 Caki-1 cells nationallicence Perfused rat heart nationallicence Uptake2 nationallicence Membrane potential nationallicence Noradrenaline nationallicence COMT : catechol-O-methyl transferase nationallicence DOMA : dihydroxymandelic acid nationallicence DOPEG : dihydroxyphenylglycol nationallicence MAO : monoamine oxidase nationallicence NMN : normetanephrine nationallicence OMDA : O-methylated and deaminated metabolites nationallicence Schömig E. Institut für Pharmakologie und Toxikologie, Universität Würzburg, Versbacher Strasse 9, W-8700, Würzburg, Germany aut Babin-Ebell J. Institut für Pharmakologie und Toxikologie, Universität Würzburg, Versbacher Strasse 9, W-8700, Würzburg, Germany aut Russ H. Institut für Pharmakologie und Toxikologie, Universität Würzburg, Versbacher Strasse 9, W-8700, Würzburg, Germany aut Trendelenburg U. Institut für Pharmakologie und Toxikologie, Universität Würzburg, Versbacher Strasse 9, W-8700, Würzburg, Germany aut Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 345/4(1992-04-01), 437-443 0028-1298 345:4<437 1992 345 210 https://doi.org/10.1007/BF00176622 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00176622 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Schömig E. Institut für Pharmakologie und Toxikologie, Universität Würzburg, Versbacher Strasse 9, W-8700, Würzburg, Germany aut NATIONALLICENCE 700 1- Babin-Ebell J. Institut für Pharmakologie und Toxikologie, Universität Würzburg, Versbacher Strasse 9, W-8700, Würzburg, Germany aut NATIONALLICENCE 700 1- Russ H. Institut für Pharmakologie und Toxikologie, Universität Würzburg, Versbacher Strasse 9, W-8700, Würzburg, Germany aut NATIONALLICENCE 700 1- Trendelenburg U. Institut für Pharmakologie und Toxikologie, Universität Würzburg, Versbacher Strasse 9, W-8700, Würzburg, Germany aut NATIONALLICENCE 773 0- Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 345/4(1992-04-01), 437-443 0028-1298 345:4<437 1992 345 210 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer