[47] Measuring uptake rates in intact tissue

Ma, Bunin; Rm, Wightman

doi:10.1016/s0076-6879(98)96049-9

Cited by 15 publications

(12 citation statements)

References 43 publications

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“…Examples of promiscuous uptake include uptake of DA into NE neurons, DA uptake into 5‐HT neurons, and NE uptake into 5‐HT neurons (Carboni et al,1990; Shen et al,2004; Vizi et al,2004). In vivo voltametry measurements of synaptic 5‐HT in brain show high concentrations of about 6 mM (Bunin and Wightman,1998), and the neurotransmitter needs to diffuse greater than 20 μm away from the synaptic cleft before the concentration of 5‐HT falls to the micromolar and then nanomolar range. The neurotransmitter levels in the micromolar concentration range as shown in that study are high enough to undergo heterologous uptake even though the non‐native transporters have relatively low affinity for the non‐native neurotransmitter (Daws,2009).…”

Section: Discussionmentioning

confidence: 99%

Identification of genes involved in the ciliary trafficking of C. elegans PKD‐2

Bae

Lyman-Gingerich

Barr

et al. 2008

Developmental Dynamics

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Ciliary membrane proteins are important extracellular sensors, and defects in their localization may have profound developmental and physiological consequences. To determine how sensory receptors localize to cilia, we performed a forward genetic screen and identified eleven mutants with defects in the ciliary localization (cil) of C. elegans PKD-2, a transient receptor potential polycystin (TRPP) channel. Class A cil mutants exhibit defects in PKD-2::GFP somatodendritic localization while Class B cil mutants abnormally accumulate PKD-2::GFP in cilia. Further characterization reveals that some genes mutated in cil mutants act in a tissue-specific manner while others are likely to play more general roles in such processes as intraflagellar transport (IFT). To this end we identified a Class B mutation that disrupts the function of the cytoplasmic dynein light intermediate chain gene xbx-1. Identification of the remaining mutations will reveal novel molecular pathways required for ciliary receptor localization and provide further insight into mechanisms of ciliary signaling.

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Section: Discussionmentioning

confidence: 99%

Identification of genes involved in the ciliary trafficking of C. elegans PKD‐2

Bae

Lyman-Gingerich

Barr

et al. 2008

Developmental Dynamics

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“…Electrochemical techniques are also used to measure extracellular monoamine levels and infer rates of uptake/MA clearance (Bunin and Wightman, 1998;Reed et al, 2003;Daws and Toney, 2007). These techniques involve the oxidation of monoamines by a carbon fiber probe (fiber or rotating disk) with substrate concentration at the electrode surface determined as a function of time from the oxidation current.…”

Section: A Monitoring Transporter Functionmentioning

confidence: 99%

Kinase-dependent Regulation of Monoamine Neurotransmitter Transporters

Bermingham

Blakely

2016

Pharmacol Rev

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“…Examples of promiscuous uptake include uptake of DA into NE neurons, DA uptake into 5-HT neurons, and NE uptake into 5-HT neurons (Carboni et al, 1990;Shen et al, 2004;Vizi et al, 2004). In vivo voltametry measurements of synaptic 5-HT in brain show high concentrations of about 6 mM (Bunin and Wightman, 1998), and the neurotransmitter needs to diffuse greater than 20 lm away from the synaptic cleft before the concentration of 5-HT falls to the micromolar and then nanomolar range. The neurotransmitter levels in the micromolar concentration range as shown in that study are high enough to undergo heterologous uptake even though the nonnative transporters have relatively low affinity for the non-native neurotransmitter (Daws, 2009).…”

Section: Role Of Heterologous Uptake Inhibition In the Activity Of A Trimentioning

confidence: 99%

Effects of the triple reuptake inhibitor amitifadine on extracellular levels of monoamines in rat brain regions and on locomotor activity

Gołembiowska

Kowalska

Bymaster³

2012

Synapse

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Major depressive disorder is a prevalent disease, and current pharmacotherapy is considered to be inadequate. It has been hypothesized that a triple reuptake inhibitor (TRI) that activates dopamine (DA) neurotransmission in addition to serotonin and norepinephrine (NE) circuitries may result in enhanced antidepressant effects. Here, we investigated the pharmacological effects of a serotonin-preferring TRI-amitifadine (EB-1010, formerly DOV 21947). The effects of amitifadine (10 mg/kg ip.) on extracellular concentrations of monoamines and their metabolites in rat brain regions were investigated using the in vivo microdialysis technique. The effects of amitifadine on locomotor activity and stereotyped behavior were also evaluated. A major metabolite of amitifadine, the 2-lactam compound, was investigated for inhibition of monoamine uptake processes. Amitifadine markedly and persistently increased extracellular concentrations of serotonin, NE, and DA in prefrontal cortex. The extracellular concentrations of DA were also increased in the DA-rich areas striatum and nucleus accumbens. The extracellular concentrations of the metabolites of serotonin, 5-hydroxyindoleacetic acid, and DA, 3,4-dihydroxyphenylacetic and homovanillic acid, were also markedly decreased in brain regions. Amitifadine did not increase locomotor activity or stereotypical behaviors over a broad dose range. The lactam metabolite of amitifadine weakly inhibited monoamine uptake. Thus, amitifadine increased extracellular concentrations of serotonin, NE, and DA, consistent with TRI. Although amitifadine significantly increased DA in the nucleus accumbens, it did not induce locomotor hyperactivity or stereotypical behaviors. The enhancement of serotonin, NE, and DA in rat brain regions associated with depression suggest that amitifadine may have novel antidepressant activity.

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[47] Measuring uptake rates in intact tissue

Cited by 15 publications

References 43 publications

Identification of genes involved in the ciliary trafficking of C. elegans PKD‐2

Identification of genes involved in the ciliary trafficking of C. elegans PKD‐2

Kinase-dependent Regulation of Monoamine Neurotransmitter Transporters

Effects of the triple reuptake inhibitor amitifadine on extracellular levels of monoamines in rat brain regions and on locomotor activity

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