IPF, a vesicular uptake inhibitory protein factor, can reduce the Ca<sup>2+</sup>‐dependent, evoked release of glutamate, GABA and serotonin

Tsutsumi, Yutaka; Özkan, Eric D.; Bole, David G.; Ueda, Tetsufumi

doi:10.1046/j.1471-4159.2001.00120.x

Cited by 20 publications

(15 citation statements)

References 93 publications

(97 reference statements)

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“…One of the more interesting discoveries among VGLUT inhibitors is the discovery of a protein capable of blocking glutamate uptake [10,65]. Inhibitory protein factor (IPF) is an endogenous inhibitor found in the synaptosomal cytosol that can halt glutamate [and GABA accumulation] into isolated vesicles with an IC 50 value of 24 nM [10].…”

Section: Alkaloids Protein Inhibitorsmentioning

confidence: 99%

Inhibitors of the Glutamate Vesicular Transporter (VGLUT)

Thompson¹,

Davis²,

Carrigan³

et al. 2005

CMC

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The vesicular glutamate transporter (VGLUT) is responsible for the uptake of the excitatory amino acid, L-glutamate, into synaptic vesicles. VGLUT activity is coupled to an electrochemical gradient driven by a vacuolar ATPase and stimulated by low Cl-. VGLUT has relatively low affinity (K(m) = 1-3 mM) for glutamate and is pharmacologically and structurally distinct from the Na+-dependent, excitatory amino acid transporters (EAATs) found on the plasma membrane. Because glutamatergic neurotransmission begins with vesicular release, compounds that block the uptake of glutamate into the vesicle may reduce excitotoxic events. Several classes of competitive VGLUT inhibitors have emerged including amino acids and amino acid analogs, fatty acids, azo dyes, quinolines and alkaloids. The potency with which these agents inhibit VGLUT varies from millimolar (amino acids) to nanomolar (azo dyes) concentrations. These inhibitors represent highly diverse structures and have collectively begun to reveal key pharmacophore elements that may elucidate the key interactions important to binding VGLUT. Using known inhibitor structures and preliminary molecular modeling, a VGLUT pharmacophore is presented that will aid in the design of new, highly potent and selective agents.

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Section: Alkaloids Protein Inhibitorsmentioning

confidence: 99%

Inhibitors of the Glutamate Vesicular Transporter (VGLUT)

Thompson¹,

Davis²,

Carrigan³

et al. 2005

CMC

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“…Thus, it was shown able to suppress the amount of glutamate released by exocytosis [165]. However, both IPF and Rose Bngal exhibited potent inhibition of vesicular uptake of GABA and serotonin as well [160,164,167,171]. Thus, these agents proved non-specific to VGLUT.…”

Section: Glutamate Release Regulation Via Modulation Of Vglut Activitmentioning

confidence: 99%

“…A number of VGLUT inhibitors have been reported [52,62,70,94,[157][158][159][160][161][162][163][164][165][166][167][168][169][170]172]. However, only three inhibitors have been shown capable of downregulating the amount of exocytotically released glutamate: the vesicular transmitter uptake inhibitory protein factor (IPF) [164], Rose Bengal [165], and ketone bodies, in particular acetoacetic acid [70]. IPF is a potent VGLUT inhibitor with a high molecular weight and an elongated shape [160].…”

Section: Glutamate Release Regulation Via Modulation Of Vglut Activitmentioning

confidence: 99%

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Glutamate Release

Hackett

Ueda

2015

Neurochem Res

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Our aim was to review the processes of glutamate release from both biochemical and neurophysiological points of view. A large body of evidence now indicates that glutamate is specifically accumulated into synaptic vesicles, which provides strong support for the concept that glutamate is released from synaptic vesicles and is the major excitatory neurotransmitter. Evidence suggests the notion that synaptic vesicles, in order to sustain the neurotransmitter pool of glutamate, are endowed with an efficient mechanism for vesicular filling of glutamate. Glutamate-loaded vesicles undergo removal of Synapsin I by CaM kinase II-mediated phosphorylation, transforming to the release-ready pool. Vesicle docking to and fusion with the presynaptic plasma membrane are thought to be mediated by the SNARE complex. The Ca(2+)-dependent step in exocytosis is proposed to be mediated by synaptotagmin.

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“…This protein appears to be concentrated in synaptosomal cytosol and also interferes with glutamate, GABA ,and serotonin release probably due to an impaired uptake (Tamura et al 2001). IPF could be one of the cytosolic factors involved in the G protein-mediated transmitter transporter downregulation.…”

Section: Modulation Of Transporter Activity By Cytosolic Componentsmentioning

confidence: 99%

Regulation of vesicular neurotreansmitter transporters

Ahnert‐Hilger

Höltje

Pahner

et al.

Reviews of Physiology, Biochemistry and Pharmacology

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Neurotransmitters are key molecules of neurotransmission. They are concentrated first in the cytosol and then in small synaptic vesicles of presynaptic terminals by the activity of specific neurotransmitter transporters of the plasma and the vesicular membrane, respectively. It has been shown that postsynaptic responses to single neurotransmitter packets vary over a wide range, which may be due to a regulation of vesicular neurotransmitter filling. Vesicular filling depends on the availability of transmitter molecules in the cytoplasm and the active transport into secretory vesicles relying on a proton gradient. In addition, it is modulated by vesicle-associated heterotrimeric G proteins, Galphao2 and Galphaq, which regulate VMAT activities in brain and platelets, respectively, and may also be involved in the regulation of VGLUTs. It appears that the vesicular content activates the G protein, suggesting a signal transduction form the luminal site which might be mediated by a vesicular G-protein coupled receptor or, as an alternative, possibly by the transporter itself. These novel functions of G proteins in the control of transmitter storage may link regulation of the vesicular content to intracellular signal cascades.

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IPF, a vesicular uptake inhibitory protein factor, can reduce the Ca²⁺‐dependent, evoked release of glutamate, GABA and serotonin

Cited by 20 publications

References 93 publications

Inhibitors of the Glutamate Vesicular Transporter (VGLUT)

Inhibitors of the Glutamate Vesicular Transporter (VGLUT)

Glutamate Release

Regulation of vesicular neurotreansmitter transporters

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IPF, a vesicular uptake inhibitory protein factor, can reduce the Ca2+‐dependent, evoked release of glutamate, GABA and serotonin

Cited by 20 publications

References 93 publications

Inhibitors of the Glutamate Vesicular Transporter (VGLUT)

Inhibitors of the Glutamate Vesicular Transporter (VGLUT)

Glutamate Release

Regulation of vesicular neurotreansmitter transporters

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Product

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IPF, a vesicular uptake inhibitory protein factor, can reduce the Ca²⁺‐dependent, evoked release of glutamate, GABA and serotonin