A molecular analysis of vesicular amine transport

Liu, Yongjian; Peter, Doris; Merickel, A.; Krantz, David E.; Finn, James P.; Edwards, Robert H.

doi:10.1016/0166-4328(96)00069-1

Cited by 22 publications

(14 citation statements)

References 62 publications

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“…Indeed, granule swelling indicative of reduced association is observed upon egress of 5-HT from the granule (10). 5-HT release could be further modulated by the increased cytoplasmic histamine because it also can inhibit VMAT2-mediated 5-HT transport (25). Thus, with both reduced VMAT2 number and its pharmacological inhibition, we find that 5-HT is depleted to a greater degree than histamine.…”

Section: Discussionmentioning

confidence: 67%

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Differential quantal release of histamine and 5-hydroxytryptamine from mast cells of vesicular monoamine transporter 2 knockout mice

Travis¹,

Wang

Michael³

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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The recent availability of mice lacking the neuronal form of the vesicular monoamine transporter 2 (VMAT2) affords the opportunity to study its roles in storage and release. Carbon fiber microelectrodes were used to measure individual secretory events of histamine and 5-hydroxytryptamine (5-HT) from VMAT2-expressing mast cells as a model system for quantal release. VMAT2 is indispensable for monoamine storage because mast cells from homozygous (VMAT2 ؊/؊ ) mice, while undergoing granule-cell fusion, do not release monoamines. Cells from heterozygous animals (VMAT2 ؉/؊ ) secrete lower amounts of monoamine per granule than cells from wild-type controls. Investigation of corelease of histamine and 5-HT from granules in VMAT2 ؉/؊ cells revealed 5-HT quantal size was reduced more than that of histamine. Thus, although vesicular transport is the limiting factor determining quantal size of 5-HT and histamine release, intragranular association with the heparin matrix also plays a significant role.

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Section: Discussionmentioning

confidence: 67%

“…Two subtypes of monoamine transporter (VMAT1 and VMAT2) have been cloned and characterized (22)(23)(24)(25). The mutant mice used in this work lack the neuronal isoform VMAT2 (5,15,26).…”

Section: Discussionmentioning

confidence: 99%

Differential quantal release of histamine and 5-hydroxytryptamine from mast cells of vesicular monoamine transporter 2 knockout mice

Travis¹,

Wang

Michael³

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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“…Consequently, these neurons express the proteins necessary to produce and use NE as a transmitter including the vesicular monoamine transporter 2 (VMAT2) in addition to neuropeptide Y (NPY; Romeo et al, 1994;Liu et al, 1996;Headley et al, 2007). However, sympathetic neurons demonstrate plasticity in regard to transmitter expression under certain circumstances.…”

Section: Introductionmentioning

confidence: 99%

Segregation of the classical transmitters norepinephrine and acetylcholine and the neuropeptide Y in sympathetic neurons: Modulation by ciliary neurotrophic factor or prolonged growth in culture

Vega

Luther

Birren

et al. 2010

Developmental Neurobiology

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Recent evidence has demonstrated that cotransmission from mammalian neurons is not uniquely achieved by costorage and corelease of transmitters and cotransmitters from single varicosities, but also by the concurrent release of mediators segregated in separate synapses of individual neurons. An important question to be addressed is whether neurons show defined patterns of segregation or whether this is a plastic feature. We addressed this question by exploring the segregation pattern of the classical sympathetic transmitters norepinephrine (NE) and acetylcholine (ACh) and the cotransmitter neuropeptide Y (NPY) in sympathetic ganglionic neurons cocultured with cardiac myocytes. Using antibodies against NPY and the vesicular NE and ACh transporters VMAT2 and vesicular acetylcholine transporter (VAChT), we investigated the effect of ciliary neurotrophic factor (CNTF) or long (three weeks) culture periods on the segregation of VMAT2, VAChT, and NPY to separate varicosities. We found that although ganglionic neurons showed cell body coexpression of all the markers examined after three days, VMAT2 was segregated from VAChT in 43% of the VAChT-positive varicosities. In contrast, VMAT2 was only segregated from NPY in 16.3% of the NPY-positive varicosities. Cotransmitter segregation and VAChT expression was potentiated by both CNTF and longer times in culture. We also found two types of varicosities: one was smaller and located further from neuronal somata, and the other was larger, proximal to neuronal somata and had a higher level of segregation. These data demonstrate segregation of classical transmitters in sympathetic neurons and plasticity of neurotransmitter segregation. Finally, we discuss a possible functional correlate of segregation in sympathetic neurons.

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“…In the extravesicular cytoplasmic compartments of dopaminergic neurons, DA can produce free radicals and/or form adducts with important cellular proteins that can contribute to cellular stress and damage (Uhl, 1998). Extravesicular cytoplasmic DA concentrations are regulated by the serial actions of two transporters: the plasma membrane dopamine transporter (DAT), which mediates neuronal uptake of DA from extracellular spaces into this compartment (Giros et al, 1992; Kilty et al, 1991; Nirenberg et al, 1996b; Shimada et al, 1991; Usdin et al, 1991), and the vesicular monoamine transporter 2 (VMAT2), which translocates DA from this extravesicular cytoplasmic compartment into synaptic vesicles (Erickson et al, 1992; Gonzalez et al, 1994; Liu et al, 1994; Liu et al, 1996; Liu et al, 1992; Merickel et al, 1995; Nirenberg et al, 1996a; Peter et al, 1996; Peter et al, 1995; Roghani et al, 1996; Surratt et al, 1993; Takahashi and Uhl, 1997). Amphetamine-like compounds block VMAT2-mediated transport of DA into synaptic vesicles, elevating extravesicular cytoplasmic DA levels and releasing DA via mechanisms that include DAT-mediated reverse transport.…”

Section: Introductionmentioning

confidence: 99%

Decreased vesicular monoamine transporter 2 (VMAT2) and dopamine transporter (DAT) function in knockout mice affects aging of dopaminergic systems

et al. 2014

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Dopamine (DA) is accumulated and compartmentalized by the dopamine transporter (DAT; SLC3A6) and the vesicular monoamine transporter 2 (VMAT2; SLC18A2). These transporters work at the plasma and vesicular membranes of dopaminergic neurons, respectively, and thus regulate levels of DA in neuronal compartments that include the extravesicular cytoplasmic compartment. DA in this compartment has been hypothesized to contribute to oxidative damage that can reduce the function of dopaminergic neurons in aging brains and may contribute to reductions in dopaminergic neurochemical markers, locomotor behavior and responses to dopaminergic drugs that are found in aged animals. The studies reported here examined aged mice with heterozygous deletions of VMAT2 or of DAT, which each reduce transporter expression to about 50% of levels found in wild-type (WT) mice. Aged mice displayed reduced locomotor responses under a variety of circumstances, including in response to locomotor stimulants, as well as changes in monoamine levels and metabolites in a regionally dependent manner. Several effects of aging were more pronounced in heterozygous VMAT2 knockout (KO) mice, including aging induced reductions in locomotion and reduced locomotor responses to cocaine. By contrast, some effects of aging were reduced or not observed in heterozygous DAT KO mice. These findings support the idea that altered DAT and VMAT2 expression affect age-related changes in dopaminergic function. These effects are most likely mediated by alterations in DA compartmentalization, and might be hypothesized to be more exacerbated by other factors that affect the metabolism of cytosolic DA.

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A molecular analysis of vesicular amine transport

Cited by 22 publications

References 62 publications

Differential quantal release of histamine and 5-hydroxytryptamine from mast cells of vesicular monoamine transporter 2 knockout mice

Differential quantal release of histamine and 5-hydroxytryptamine from mast cells of vesicular monoamine transporter 2 knockout mice

Segregation of the classical transmitters norepinephrine and acetylcholine and the neuropeptide Y in sympathetic neurons: Modulation by ciliary neurotrophic factor or prolonged growth in culture

Decreased vesicular monoamine transporter 2 (VMAT2) and dopamine transporter (DAT) function in knockout mice affects aging of dopaminergic systems

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