Uptake and metabolism of γ-aminobutyric acid by neurones and glial cells

Iversen, Leslie L.; Kelly, John T.

doi:10.1016/0006-2952(75)90422-0

Cited by 564 publications

(193 citation statements)

References 57 publications

Supporting

Mentioning

180

Contrasting

Unclassified

Order By: Relevance

“…The procedure of Iversen & Kelly (1975) was used. Immediately after decapitation, the tissues were dissected and cut into 100pm thick slices using a tissue sectioner (Smith & Farquhar Sorvall TC-2) and incubated at 370C in 5 ml Krebs solution (bubbled with 95% 02:5% C02) for 15min before the addition of [3H]-GABA (0.4ymoll 1, specific activity 0.65Cimmol-1).…”

Section: Uptake Of [3h]-gabamentioning

confidence: 99%

Acute stress and GABAergic function in the rat brain

Losada

1989

British J Pharmacology

View full text Add to dashboard Cite

1 The function of the y-aminobutyric acid (GABA)-ergic system in certain areas of the rat brain was investigated after acute (5 min) exposure to immobilization stress. 2 The activities of glutamate decarboxylase and GABA-transaminase, GABA concentrations, GABA turnover in vivo and uptake of [3H]-GABA were measured. 3 After 5min of immobilization stress, GABA concentrations and [3H]-GABA uptake were reduced, and GABA turnover stimulated in the olfactory bulbs. In contrast the uptake of [3H]-GABA was increased in the corpus striatum after 5 min of immobilization stress. 4 None of the parameters measured was significantly altered by acute immobilization stress in the frontal cortex, hippocampus or medio-basal hypothalamus. 5 These findings show that the olfactory bulbs and the corpus striatum are sensitive to the effects of acute stress. Since GABA in the olfactory bulbs is involved in the development of aggression and increased emotional state, it follows that neurochemical changes induced by acute stress might underlie some behavioural manifestations observed after stress.

show abstract

Section: Uptake Of [3h]-gabamentioning

confidence: 99%

Acute stress and GABAergic function in the rat brain

Losada

1989

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…Neurotransmitter transporters control these levels by reuptake of excess neurotransmitters from the synapse into presynaptic cells or glial cells. 2,3 These secondary transporters typically use the flow of Na + (with or without Cl − ions) down its electrochemical gradient across the cell membrane to drive the (co)transport of neurotransmitters (or substrate) against their concentration gradient, 4 hence their family name neurotransmitter:sodium symporter (NSS). The NSS a) Author to whom correspondence should be addressed.…”

Section: Introductionmentioning

confidence: 99%

Energy landscape of LeuT from molecular simulations

Gür

Zomot

Cheng

et al. 2015

The Journal of Chemical Physics

View full text Add to dashboard Cite

The bacterial sodium-coupled leucine transporter (LeuT) has been broadly used as a structural model for understanding the structure-dynamics-function of mammalian neurotransmitter transporters as well as other solute carriers that share the same fold (LeuT fold), as the first member of the family crystallographically resolved in multiple states: outward-facing open, outward-facing occluded, and inward-facing open. Yet, a complete picture of the energy landscape of (sub)states visited along the LeuT transport cycle has been elusive. In an attempt to visualize the conformational spectrum of LeuT, we performed extensive simulations of LeuT dimer dynamics in the presence of substrate (Ala or Leu) and co-transported Na + ions, in explicit membrane and water. We used both conventional molecular dynamics (MD) simulations (with Anton supercomputing machine) and a recently introduced method, collective MD, that takes advantage of collective modes of motions predicted by the anisotropic network model. Free energy landscapes constructed based on ∼40 µs trajectories reveal multiple substates occluded to the extracellular (EC) and/or intracellular (IC) media, varying in the levels of exposure of LeuT to EC or IC vestibules. The IC-facing transmembrane (TM) helical segment TM1a shows an opening, albeit to a smaller extent and in a slightly different direction than that observed in the inward-facing open crystal structure. The study provides insights into the spectrum of conformational substates and paths accessible to LeuT and highlights the differences between Ala-and Leu-bound substates. C 2015 AIP Publishing LLC. [http://dx

show abstract

“…Key words: Procambarus clarkii; crustaceans; crayfish; X-organ sinus gland system; peptidergic neurons; GABA transporters; GABA A receptors GABA is the major inhibitory neurotransmitter in both the CNS and PNS of vertebrates (Iversen and Kelly, 1975;Martin, 1976) and invertebrates (Iversen and Kravitz, 1968;Kerkut et al, 1969;Sattelle, 1990). After the neurotransmitter has been released, its postsynaptic action must be terminated by activation of a sodiumdependent high-affinity GABA uptake system, which is present in presynaptic terminals and glial cells (Atwood, 1976;Krnjevic, 1984;Erecinska, 1987;Kanner and Schuldiner, 1987;Dingledine et al, 1988).…”

mentioning

confidence: 99%

Expression and Functional Characterization of GABA Transporters in Crayfish Neurosecretory Cells

et al. 2002

View full text Add to dashboard Cite

The effect of GABA on membrane potential and ionic currents of X-organ neurons isolated from the crayfish eyestalk was investigated. Under voltage-clamp conditions, GABA elicited an inward Na ϩ current followed by a sustained outward chloride current. Sodium current was partially blocked in a dose-dependent manner by antagonists of GABA plasma membrane transporters such as ␤-alanine, nipecotic acid, 1-[2([(diphenylmethylene)imino]oxy)ethyl]-1,2,5,6-tetrahydro-3-pyridinecarboxylic acid hydrochloride (NO 711), and SKF89976-A at concentrations between 1 and 100 M. This current was totally blocked by the combined application of NO 711 (5 M) and ␤-alanine (50 M). We obtained an EC 50 of 5 M and a Hill coefficient of 0.97 for the GABA transport mediated response. These results together with studies of immunolocalization using antibodies against neuronal vertebrate GABA transporters (GATs) indicate the presence of GAT-1-and GAT-3-like proteins in X-organ neurons. To isolate the sustained outward Cl Ϫ current, extracellular free sodium solution was used to minimize the contribution of GAT activity. We concluded that this current was caused by the activation of GABA A -like receptors with an EC 50 of 10 M and a Hill number of 1.7.To assign a functional role to the GATs in the X-organ sinus gland system, we determine the GABA concentration (0.46-0.15 M) in hemolymph samples using HPLC.In summary, our results suggest that a sodium-dependent electrogenic GABA uptake mechanism has a direct influence on the excitability of the X-organ neurons, maintaining an excitatory tone that is dependent on the circulating GABA level.

show abstract

Uptake and metabolism of γ-aminobutyric acid by neurones and glial cells

Cited by 564 publications

References 57 publications

Acute stress and GABAergic function in the rat brain

Acute stress and GABAergic function in the rat brain

Energy landscape of LeuT from molecular simulations

Expression and Functional Characterization of GABA Transporters in Crayfish Neurosecretory Cells

Contact Info

Product

Resources

About