Summary
Experiments were carried out with hearts isolated from reserpine- and pargyline-pretreated rats; both noradrenaline-metabolizing enzymes and uptake1 were inhibited. Initial rates of extraneuronal uptake were measured after perfusion lasting for 2 min, either in the absence or in the presence of 100 μmol/l O-methyl-isoprenaline, a potent inhibitor of uptake2.
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1.
The ID50 (i.e., the concentration of unlabelled substance that halves the rate of uptake of a tracer concentration of 3H-(±)-isoprenaline) was determined for a variety of agents. Two types of stereoselective preference of (-)-isomers were observed: for isoprenaline and adrenaline (but not for noradrenaline)-and also for dobutamine.
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2.
The stereoselective preference for the (-)-isomers of isoprenaline and adrenaline is also evident from fluorimetric determination of initial rates of uptake of unlabelled isomers.
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3.
Experiments with various tritiated compounds indicate that uptake2 has a broad substrate spectrum: uptake2 is not restricted to 3H-catecholamines and 3H-phenethylamines, but extends to resorcinols (3H-orciprenaline), imidazoline derivatives (3H-clonidine), 3H-histamine and 3H-5-hydroxytryptamine (3H-5-HT).
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4.
Determinations of the V max of uptake2 revealed a correlation between the ID50 and the V max: the higher the ID50, the higher the V max.
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5.
These results indicate that uptake2 is a carrier-mediated process.
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Supported by the Deutsche Forschungsgemeinschaft (Tr 96). A preliminary report of some of the findings was presented to the German Pharmacological Society (Grohmann et al. 1983).
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Grohmann, M., Trendelenburg, U. The substrate specificity of uptake2 in the rat heart. Naunyn-Schmiedeberg's Arch. Pharmacol. 328, 164–173 (1984). https://doi.org/10.1007/BF00512067
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DOI: https://doi.org/10.1007/BF00512067