caa a22 4500 469079320 CHVBK 20180323132945.0 cr unu---uuuuu 170328e19920301xx s 000 0 eng 10.1007/BF00168693 doi (NATIONALLICENCE)springer-10.1007/BF00168693 Vascular uptake of catecholamines in perfused lungs of the rat occurs by the same process as Uptake1 in noradrenergic neurones [Elektronische Daten] [Lesley Bryan-Lluka, Nicola Westwood, Stella O'Donnell] Summary: The aim of the study was to determine whether the uptake process for catecholamines in rat lungs is Uptake1, Uptake2 or a distinct process with some properties of both Uptake1 and Uptake2. The initial rate of uptake of noradrenaline was measured in isolated lungs of rats perfused with 2 nmol/l 3H-(−)-noradrenaline for 2 min with monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) inhibited, in the absence or presence of drugs that are substrates or inhibitors of Uptake1 or Uptake2 or of alterations in the ionic composition of the Krebs solution. The rank order of the IC50 values for inhibition of uptake of noradrenaline in the lungs by drugs that are substrates or inhibitors of Uptake1 or Uptake2 is compatible with the conclusion that uptake of catecholamines in rat lungs occurs by Uptake2, and not by a process with the properties of Uptake2. Additional evidence was provided by the marked inhibition of uptake in the lungs when the Na+ concentration in the Krebs solution was decreased from 143 to 25 mmol/l and by the lack of inhibition when the K+ concentration was increased from 5.9 mmol/l to either 10.9 or 20.9 mmol/1. Further experiments were included in the study to obtain data additional to histological evidence (Hughes et al. 1969; Nicholas et al. 1974) regarding the site of Uptake1 in rat lungs. Pretreatment of rats with either 6-hydroxydopamine (to destroy noradrenergic neurones) or reserpine (to inhibit synaptic vesicle uptake) had no effect on the deamination or accumulation of noradrenaline in lungs perfused with 3H-noradrenaline (COMT inhibited). In a further series of experiments, efflux of noradrenaline from rat lungs, after loading with 3H-noradrenaline (MAO and COMT inhibited), could be described by a single compartment with a half-time for efflux of 42 min and with no "bound fraction”. These results provide further evidence that no significant uptake of noradrenaline in the lungs occurs into noradrenergic neurones and are compatible with histological evidence that the endothelial cells of the lung microvasculature are the site of noradrenaline uptake. The study has shown that the uptake of catecholamines in the lungs, at least in the rat, occurs by Uptake1, and hence the pulmonary endothelial cells are a nonneuronal site where catecholamine transport occurs by Uptake1. Springer-Verlag, 1992 Rat lungs nationallicence Catecholamines nationallicence Uptake1 nationallicence Pulmonary endothelial cells nationallicence Bryan-Lluka Lesley Department of Physiology and Pharmacology, The University of Queensland, 4072, Brisbane, Queensland, Australia aut Westwood Nicola Department of Physiology and Pharmacology, The University of Queensland, 4072, Brisbane, Queensland, Australia aut O'Donnell Stella Department of Physiology and Pharmacology, The University of Queensland, 4072, Brisbane, Queensland, Australia aut Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 345/3(1992-03-01), 319-326 0028-1298 345:3<319 1992 345 210 https://doi.org/10.1007/BF00168693 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00168693 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Bryan-Lluka Lesley Department of Physiology and Pharmacology, The University of Queensland, 4072, Brisbane, Queensland, Australia aut NATIONALLICENCE 700 1- Westwood Nicola Department of Physiology and Pharmacology, The University of Queensland, 4072, Brisbane, Queensland, Australia aut NATIONALLICENCE 700 1- O'Donnell Stella Department of Physiology and Pharmacology, The University of Queensland, 4072, Brisbane, Queensland, Australia aut NATIONALLICENCE 773 0- Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 345/3(1992-03-01), 319-326 0028-1298 345:3<319 1992 345 210 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer