Vascular uptake of catecholamines in perfused lungs of the rat occurs by the same process as Uptake1 in noradrenergic neurones

Bryan-Lluka L.J., Westwood N.N. and O'Donnell S.R. (1992) Vascular uptake of catecholamines in perfused lungs of the rat occurs by the same process as Uptake1 in noradrenergic neurones. Naunyn-Schmiedeberg's Archives of Pharmacology, 345 3: 319-326. doi:10.1007/BF00168693


Author Bryan-Lluka L.J.
Westwood N.N.
O'Donnell S.R.
Title Vascular uptake of catecholamines in perfused lungs of the rat occurs by the same process as Uptake1 in noradrenergic neurones
Journal name Naunyn-Schmiedeberg's Archives of Pharmacology   Check publisher's open access policy
ISSN 0028-1298
Publication date 1992-01-01
Sub-type Article (original research)
DOI 10.1007/BF00168693
Volume 345
Issue 3
Start page 319
End page 326
Total pages 8
Publisher Springer-Verlag
Subject 3004 Pharmacology
Abstract 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.
Keyword Catecholamines
Pulmonary endothelial cells
Rat lungs
Uptake1
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: Scopus Import
 
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