Inhibition of synaptosomal uptake of amino acid transmitters by diamines

Strain, George M.; Flory, W; Tucker, Terri A.

doi:10.1016/0028-3908(84)90013-3

Cited by 4 publications

(6 citation statements)

References 19 publications

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“…1(A)]. These results correspond with the reported pharmacological potency of these diamines on GABA transport activity measured in vitro: DABA inhibited GABA transport into rat brain synaptic plasma membrane vesicles isolated from rat brain more effectively than a related series of diaminopropanoic analogues (Strain et al, 1984). Our results suggest that the affinities of the Drosophila transporters for these GABA analogs may be similar to those of vertebrate species.…”

Section: Locomotor Activitysupporting

confidence: 87%

“…DL-2,3-Diaminopropionic acid (DAPA), an aliphatic diamine, is a potent competitive inhibitor of GABA transport in mouse brain particles (Liron et al, 1988). In comparison, a series of related diaminopropionic analogues such as 1,3-diaminopropionic acid and 1,2-diaminopropionic acid inhibited rat synaptosomal GABA uptake by ϳ40 -80%, while DL-2,4diaminobutyric acid inhibited uptake by 100% (Strain et al, 1984). In our [ 3 H]-GABA uptake studies with Drosophila SPM vesicles, DAPA inhibited uptake by ϳ60% relative to DABA, which inhibited uptake by 100%.…”

Section: Pharmacologically Induced Behavioral Effects Resulted From Smentioning

confidence: 99%

“…We postulate that GABAergic signaling networks within this defined region of the central nervous system may play an important role in modulating locomotor activity. In addition, the peripheral effects of GABA on locomotor activity have been demonstrated in a wide variety Borden (1996), 2 Schousboe (2000), 3 Krogsgaard-Larsen (1980), 4 Strain et al (1984), 5 Hyden et al (1984), 6 and Fraser et al (1999). 7 Data that are not available is annotated with the abbreviation n.a.…”

Section: Conservation Of Gaba-modulated Behaviors Among Drosophila Anmentioning

confidence: 99%

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Pharmacological evidence for GABAergic regulation of specific behaviors inDrosophila melanogaster

Leal

Neckameyer

2002

J. Neurobiol.

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We have identified several GABAergic-modulated behaviors in Drosophila melanogaster by employing a pharmacological approach to disrupt GABA transporter function in vivo. Systemic treatment of adult female flies with the GABA transport inhibitors DL-2,4-diaminobutyric acid (DABA) or R,S-nipecotic acid (NipA), resulted in diminished locomotor activity, deficits in geotaxis, and the induction of convulsive behaviors with a secondary loss of the righting reflex. Pharmacological evidence suggested that the observed behavioral phenotypes were specific to disruption of GABA transporter function and GABAergic activity. The effects of GABA reuptake inhibitors on locomotor activity were dose dependent, pharmacologically distinct, and paralleled their known effects in mammalian systems. Recovery of normal locomotor activity and the righting reflex in DABA- and NipA-treated flies was achieved by coadministration of bicuculline (BIC), a GABA receptor antagonist that supresses GABAergic activity in mammals. Recovery of these behaviors was also achieved by coadministration of gabapentin, an anticonvulsant agent that interacts with mammalian GABAergic systems. Finally, behavioral effects were selective because other specific behaviors such as feeding activity and female sexual receptivity were not affected. Related pharmacological analyses performed in vitro on isolated Drosophila synaptic plasma membrane vesicles demonstrated high affinity, saturable uptake mechanisms for [3H]-GABA; further competitive inhibition studies with DABA and NipA demonstrated their ability to inhibit [3H]-GABA transport. The existence of experimentally accessible GABA transporters in Drosophila that share conserved pharmacological properties with their mammalian counterparts has resulted in the identification of specific behaviors that are modulated by GABA.

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Section: Locomotor Activitysupporting

confidence: 87%

Section: Pharmacologically Induced Behavioral Effects Resulted From Smentioning

confidence: 99%

Section: Conservation Of Gaba-modulated Behaviors Among Drosophila Anmentioning

confidence: 99%

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Pharmacological evidence for GABAergic regulation of specific behaviors inDrosophila melanogaster

Leal

Neckameyer

2002

J. Neurobiol.

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“…Total maximal accumulations of [ 3 H]-GABA (ϳ1 M) in PMVs isolated from several independent preparations of developmentally staged tissues were analyzed for comparative purposes. As development proceeded from the embryonic to second instar larval stage, a 10-fold increase in GABA accumulation was observed Krogsgaard-Larsen, 1980;Roskowski, 1981;Strain et al, 1984;Hyden et al, 1984;Mbungu et al, 1995;Borden, 1996;Fraser et al, 1999;Xiujuan et al, 1999;Schousboe, 2000;Leal and Neckameyer, 2002. Fig.…”

Section: Plasma Membrane Vesicles Isolated From Tissues Of Behavioralmentioning

confidence: 88%

“…PMVs isolated from larval tissues demonstrated high-affinity and saturable uptake mechanisms for [ 3 H]-GABA, and competitive inhibition studies of [ 3 H]-GABA transport with unlabeled GABA or the transport inhibitors, DABA, NipA, and valproic acid (VAL) displayed differential affinities. There is a striking degree of pharmacological conservation in GABA transport kinetics observed among Drosophila larvae, Drosophila adults, mammalian neurons, cloned mammalian GABA transporters, and other insect GABA transporters (Krogsgaard-Larsen, 1980;Roskoski,1981;Strain et al, 1984;Mbungu et al 1995;Borden, 1996;Xiujuan et al, 1999;Schousboe, 2000;Leal and Neckameyer, 2002). We also examined the transport kinetics of [ 3 H]-GABA in PMVs isolated from behaviorally quiescent developmental stages of Drosophila, and found that [ 3 H]-GABA accumulated to significantly higher levels in pupal PMVs compared with PMVs isolated from larval or adult tissues.…”

Section: Introductionmentioning

confidence: 99%

GABAergic modulation of motor‐driven behaviors in juvenileDrosophilaand evidence for a nonbehavioral role for GABA transport

Leal¹,

Kumar²,

Neckameyer³

2004

J. Neurobiol.

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We have identified specific GABAergic-modulated behaviors in the juvenile stage of the fruit fly, Drosophila melanogaster via systemic treatment of second instar larvae with the potent GABA transport inhibitor DL-2,4-diaminobutyric acid (DABA). DABA significantly inhibited motor-controlled body wall and mouth hook contractions and impaired rollover activity and contractile responses to touch stimulation. The perturbations in locomotion and rollover activity were reminiscent of corresponding DABA-induced deficits in locomotion and the righting reflex observed in adult flies. The effects were specific to these motor-controlled behaviors, because DABA-treated larvae responded normally in olfaction and phototaxis assays. Recovery of these behaviors was achieved by cotreatment with the vertebrate GABA(A) receptor antagonist picrotoxin. Pharmacological studies performed in vitro with plasma membrane vesicles isolated from second instar larval tissues verified the presence of high-affinity, saturable GABA uptake mechanisms. GABA uptake was also detected in plasma membrane vesicles isolated from behaviorally quiescent stages. Competitive inhibition studies of [3H]-GABA uptake into plasma membrane vesicles from larval and pupal tissues with either unlabeled GABA or the transport inhibitors DABA, nipecotic acid, or valproic acid, revealed differences in affinities. GABAergic-modulation of motor behaviors is thus conserved between the larval and adult stages of Drosophila, as well as in mammals and other vertebrate species. The pharmacological studies reveal shared conservation of GABA transport mechanisms between Drosophila and mammals, and implicate the involvement of GABA and GABA transporters in regulating physiological processes distinct from neurotransmission during behaviorally quiescent stages of development.

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Distinguishing the cyanobacterial neurotoxin β-N-methylamino-l-alanine (BMAA) from its structural isomer 2,4-diaminobutyric acid (2,4-DAB)

Banack

Downing

Spáčil

et al. 2010

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Inhibition of synaptosomal uptake of amino acid transmitters by diamines

Cited by 4 publications

References 19 publications

Pharmacological evidence for GABAergic regulation of specific behaviors inDrosophila melanogaster

Pharmacological evidence for GABAergic regulation of specific behaviors inDrosophila melanogaster

GABAergic modulation of motor‐driven behaviors in juvenileDrosophilaand evidence for a nonbehavioral role for GABA transport

Distinguishing the cyanobacterial neurotoxin β-N-methylamino-l-alanine (BMAA) from its structural isomer 2,4-diaminobutyric acid (2,4-DAB)

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