The extent of neuronal re-uptake of 3H-noradrenaline in isolated vasa deferentia and atria of the rat

Schömig, Edgar; Fischer, Petra; Cl, Schönfeld; Trendelenburg, U.

doi:10.1007/bf00260604

Cited by 39 publications

(37 citation statements)

References 19 publications

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“…Hence, the results of the experiments in which Na ÷ was replaced by Li" (see above) and those with addition of substrates or inhibitors of uptake1 during efflux are all compatible with the suggestion that reuptake via uptake~ is involved in limiting the net efflux of noradrenaline and dopamine from the endothelial cells of rat lungs under normal conditions. Reuptake via uptake1 has also been reported to play an important role in limiting efflux of noradrenaline from noradrenergic neurones in a study in which the rate constants for carrier-mediated efflux, diffusional efflux and reuptake of noradrenaline in rat vas deferens and atria were calculated (Sch6mig et al 1989). In both tissues, 90% of the noradrenaline that was lost from the neurones by efflux was recovered by reuptake, so that net efflux from the tissue represented only 10% of the total efftux from the neurones (Sch6mig et al i989).…”

Section: Discussionmentioning

confidence: 99%

“…However, the rate constant for noradrenaline efftux from rat lungs (0.0163 min -z) is much greater than that for noradrenaline efflux from noradrenergic neurones (vesicular uptake inhibited) of rat vas deferens (Stefano and Trendelenburg 1984;Sch6mig et al 1989) and rat atria (Sch/Smig et al 1989). It is possible that the differences between the rate constants for net efflux can be explained by differing contributions of uptake1, diffusion and reuptake to the measured net efflux.…”

Section: Discussionmentioning

confidence: 99%

“…It is possible that the differences between the rate constants for net efflux can be explained by differing contributions of uptake1, diffusion and reuptake to the measured net efflux. As discussed above, the contributions of these factors were determined in the study of Sch6mig et al (1989), but have not been determined in rat lungs. Additional possible explanations for the differences between the rate constants for efflux from pulmonary endothelial cells and noradrenergic neurones include a) some remaining contribution of the synaptic vesicles in determining the values obtained for neuronal efflux, despite treatment with reserpine; b) the large surface area to volume ratio of the flat endothelial cells which would favour efflux, particularly the diffusional component; and c) the minimal diffusional barrier for catecholamines leaving the endothelial cells in the perfused lungs, compared with cells in less intimate contact with the incubation or perfusion solution.…”

Section: Discussionmentioning

confidence: 99%

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Evidence for uptake1-mediated efflux of catecholamines from pulmonary endothelial cells of perfused lungs of rats

Westwood

Scarcella

Bryan-Lluka

1996

Naunyn-Schmiedeberg's Arch Pharmacol

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Previous pharmacological studies have demonstrated that pulmonary endothelial cells and noradrenergic neurones possess the same transporter for inward transport of catecholamines, uptake1. In noradrenergic neurones, it has been shown that uptake1 is also involved in the carrier-mediated outward transport, or efflux, of noradrenaline and dopamine. The aim of the present study was to examine the efflux of noradrenaline and dopamine from perfused lungs of rats to determine whether uptake1, in addition to diffusion, mediates efflux of catecholamines from pulmonary vascular endothelial cells. The effects of reducing the cellular sodium gradient and of substrates and inhibitors of uptake1 on the efflux of 3H-noradrenaline and 3H-dopamine from rat lungs were measured. Isolated perfused lungs of rats (monoamine oxidase and catechol-O-methyltransferase inhibited) were loaded with 3H-(-)-noradrenaline or 3H-dopamine for 10 min followed by perfusion with either (1) a low sodium, amine-free Krebs solution, in which NaCl was replaced by either Tris.HCl or LiCl, for 15 or 10 min, respectively or (2) amine-free Krebs solution for 30 min in the absence or presence of a substrate or inhibitor of uptake1 for the last 15 min. The rate constants for spontaneous efflux of noradrenaline and dopamine from the lungs were 0.0163 min-1 and 0.0466 min-1, respectively. When NaCl was replaced by Tris.HCl during efflux, the rate constants for efflux of noradrenaline and dopamine were increased 2.5-fold and 3-fold, respectively, whereas, when NaCl was replaced by LiCl, the rate constants were increased 8-fold and 4-fold, respectively. The uptake1 substrates, dopamine (1 and 3 mumol/l) and adrenaline (40 mumol/l), both caused a rapid and marked increase in the efflux of noradrenaline, while noradrenaline (4 mumol/l) had a similar effect on the efflux of dopamine. The uptake1 inhibitors, imipramine (3 and 10 mumol/l) and nisoxetine (50 nmol/l), caused small and gradual increases in the efflux of noradrenaline and dopamine from rat lungs. These results demonstrate that efflux of noradrenaline and dopamine from rat lungs is affected by alterations in the normal sodium gradient across the cell and by drugs that interact with the uptake1 transporter. Thus, it can be concluded that the spontaneous efflux of catecholamines from pulmonary vascular endothelial cells is mediated predominantly by uptake1. In addition, efflux of catecholamines from the lungs has a diffusional component, which, combined with inhibition of reuptake, accounts for the small increase in amine efflux by inhibitors of uptake1.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Evidence for uptake1-mediated efflux of catecholamines from pulmonary endothelial cells of perfused lungs of rats

Westwood

Scarcella

Bryan-Lluka

1996

Naunyn-Schmiedeberg's Arch Pharmacol

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“…Alterna-tively, the order in which the varicosities are activated along the nerve may be important. Schomig et al (1989) have shown that the outward transport of noradrenaline was three times greater in rat atria than in vas deferens. We have observed previously that atria, like brain slice, give increased evoked overflow when exposed to cocaine (El-Mas & Hughes, 1990).…”

Section: Discussionmentioning

confidence: 91%

Effect of blockade of noradrenaline re‐uptake on evoked tritium overflow from mouse vasa deferentia and rat cortex slices

El‐Mas

Hughes

1990

British J Pharmacology

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In tissues previously incubated with [3H]‐noradrenaline exposure to cocaine (0.1 to 10 μm) or desmethylimipramine (0.01 to 1 μm) produced a concentration‐dependent increase (up to 2 fold) in electrically evoked (3 Hz, 2 ms, 20 mA, 120 s every 20 min) fractional overflow of tritium from rat brain cortex slices but not from mouse vas deferens (2.5 Hz, 2 ms, 400 mA, for 90s every 14 min). Yohimbine and idazoxan (0.01 to 1 μm) increased fractional evoked overflow of tritium by up to 2 fold; in the presence of these drugs, cocaine (10 μm) produced an increase in both tissues (up to 3.5 fold over control). In brain slice an increase in stimulation frequency (0.1, 0.5, 1, 3 and 6 Hz) decreased fractional evoked overflow of tritium per pulse but cocaine (10 μm) produced a significant enhancement at each frequency except 6 Hz. In vas deferens fractional tritium overflow per pulse changed little with increasing frequency and cocaine produced no effect. In both tissues fractional evoked overflow of tritium was dependent on the stimulation current; cocaine (10 μm) increased fractional evoked overflow from brain slice at every current tested but was without effect in vas deferens. Chromatographic separation of the released tritium showed there was little difference in the proportions of [3H]‐noradrenaline and 3H‐metabolites overflowing from the tissues. Cocaine increased the proportion of [3H]‐noradrenaline and decreased the proportion of [3H]‐DOPEG overflowing both at rest and during stimulation. In brain slice an increase in electrically evoked overflow was produced by cocaine (10 μm) whether total tritium overflow (1.8 fold), overflow of [3H]‐noradrenaline (1.8 fold) or overflow of unlabelled noradrenaline (1.8 fold) was measured. Evoked overflow from vas deferens was unaffected when assessed by any of these three methods. The mechanism responsible for this differential effect of cocaine is unclear but may involve differences in the physical relationship between release sites, reuptake sites and presynaptic autoreceptors.

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“…NET recaptures as much as 90% of released NE making it a critical mediator of NE inactivation and presynaptic catecholamine homeostasis (Schomig et al 1989). Thus, NET plays a role in controlling the intensity and duration of signal transduction (Zahniser et al 2001).…”

Section: Introductionmentioning

confidence: 99%

Haplotype architecture of the norepinephrine transporter gene SLC6A2 in four populations

et al. 2004

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The norepinephrine transporter (NET) regulates levels of monoamine neurotransmitters integral to a variety of behaviors and autonomic functions. Two SLC6A2 polymorphisms have been used in genetic association studies, generating intriguing but nondefinitive results on traits such as hypertension and mood. One of these SLC6A2 variants is functional but rare. The other is common but not informative over the entire 48 kb SLC6A2 region and is insufficient to capture the functional diversity potentially contained within any SLC6A2 region. To elucidate SLC6A2 haplotype structure and define markers sufficient to capture haplotype diversity within detected haplotype blocks, 26 single-nucleotide polymorphisms (SNPs) were genotyped in 384 individuals evenly divided across Finnish Caucasian, US Caucasian, Plains American Indian, and African American populations. Three conserved blocks, 13.6, 12.5, and 25 kb in size and showing little evidence for historical recombination were observed in all populations. Haplotype diversity in block 1 and numbers of common haplotypes were highest in African Americans, among whom 5-6 optimal markers were sufficient to maximize diversity of each block. For other populations, 2-3 markers/block sufficed, but the optimal markers differed across populations. The SLC6A2 haplotype map and 25-marker panel (excluding the monomorphic one) is a comprehensive tool for genetic linkage studies on phenotypes related to NET function.

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The extent of neuronal re-uptake of 3H-noradrenaline in isolated vasa deferentia and atria of the rat

Cited by 39 publications

References 19 publications

Evidence for uptake1-mediated efflux of catecholamines from pulmonary endothelial cells of perfused lungs of rats

Evidence for uptake1-mediated efflux of catecholamines from pulmonary endothelial cells of perfused lungs of rats

Effect of blockade of noradrenaline re‐uptake on evoked tritium overflow from mouse vasa deferentia and rat cortex slices

Haplotype architecture of the norepinephrine transporter gene SLC6A2 in four populations

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