Expression cloning of a reserpine-sensitive vesicular monoamine transporter.

Erickson, Jeffrey D.; Eiden, Lee E.; Hoffman, Beth J.

doi:10.1073/pnas.89.22.10993

Cited by 429 publications

(309 citation statements)

References 15 publications

(20 reference statements)

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“…VMAT2 is a neuronally expressed subtype of the vesicular monoamine transporter responsible for loading synaptic vesicles with the monoamine neurotransmitters serotonin, norepinephrine, dopamine, and histamine (Liu et al, 1992;Peter et al, 1994;Erickson et al, 1992Erickson et al, , 1996. Mice lacking both copies of the VMAT2 gene die during development, but heterozygotes survive and show reduced amphetamineconditioned reward, enhanced amphetamine and cocaineinduced locomotion, and enhanced MPTP toxicity (Takahashi et al, 1997;Wang et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Pharmacogenomic Evaluation of the Antidepressant Citalopram in the Mouse Tail Suspension Test

Crowley

Brodkin

Blendy

et al. 2006

Neuropsychopharmacol

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The identification of genetic variants regulating antidepressant response in human patients would allow for more individualized, rational, and successful drug treatments. We have previously identified the BALB/cJ inbred mouse strain as highly responsive to the selective serotonin reuptake inhibitor (SSRI) citalopram in the tail suspension test (TST), a widely used and well-established screening paradigm for detecting compounds with antidepressant activity. In contrast, A/J mice did not show a significant response to citalopram in this test despite exposure to equivalent plasma levels of the drug. To identify genetic determinants of this differential response, 506 F 2 mice from an intercross between BALB/cJ and A/J mice were phenotyped. Composite interval mapping of 92 mice from the phenotypic extremes revealed three loci on chromosomes 7, 12, and 19 affecting citalopram response in the TST. The quantitative trait locus (QTL) at the telomeric end of chromosome 19 showed the greatest level of significance. Three candidate genes residing in this locus include those for vesicular monoamine transporter 2 (VMAT2, slc18a2), alpha 2A adrenergic receptor (adra2a), and beta 1 adrenergic receptor (adrb1). The protein coding regions of these three genes in BALB/cJ and A/J mice were sequenced and two polymorphisms were found in VMAT2 (Leu117Pro and Ser505Pro), while the transcribed regions of adra2a and adrb1 were of identical sequence between strains. Follow-up studies are needed to determine if the VMAT2 polymorphisms are functional and if they could explain the chromosome 19 QTL. The present quantitative trait study suggests possible candidate genes for human pharmacogenetic studies of therapeutic responses to SSRIs such as citalopram.

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Section: Discussionmentioning

confidence: 99%

Pharmacogenomic Evaluation of the Antidepressant Citalopram in the Mouse Tail Suspension Test

Crowley

Brodkin

Blendy

et al. 2006

Neuropsychopharmacol

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“…Once released from the cell, amines can be subject to reuptake by another set of transporters localised to the plasma membrane (Rothman and Orci, 1992;Calakos and Scheller, 1994). Two subtypes of vesicular monoamine transporters, VMAT1 and 2, have been characterised with structural similarities, but with differences in substrate specificity and tissue distribution (Erickson et al, 1992;Liu et al, 1992;Erickson and Eiden, 1993). In a recent study, we demonstrated the differential expression of VMAT1 and 2 in gut NE tumours, reflecting specific amine production and different cellular origin of these tumours.…”

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confidence: 83%

Uptake of meta-iodobenzylguanidine in neuroendocrine tumours is mediated by vesicular monoamine transporters

et al. 2003

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The radio-iodinated noradrenaline analogue meta-iodobenzylguanidine (MIBG) can be used for scintigraphy and radiation therapy of neuroendocrine (NE). The aim of the present study was to study the importance of vesicular monoamine transporters (VMATs) for the uptake of 123 I-MIBG in NE tumours. In nude mice, bearing the human transplantable midgut carcinoid GOT1, all organs and xenografted tumours accumulated 123 I after i.v. injection of 123 I-MIBG. A high concentration of 123 I was maintained in GOT1 tumours and adrenals, which expressed VMATs, but rapidly decreased in all other tissues. In the VMAT-expressing NE tumour cell lines GOT1 and BON and in VMAT-expressing primary NE tumour cell cultures (carcinoids, n ¼ 4 and pheochromocytomas, n ¼ 4), reserpine significantly reduced the uptake of 123 I-MIBG. The membrane pump inhibitor clomipramine had no effect on the uptake of 123 I-MIBG in GOT1 and BON cells, but inhibited the uptake in one out of four primary carcinoid cell cultures and three out of four primary pheochromocytoma cell cultures. In conclusion, VMATs and secretory granules are of importance for the uptake and retention of 123 I-MIBG in NE tumours. Information about the type and degree of expression of VMATs in NE tumours may be helpful in future to select patients suitable for radiation therapy with radio-iodinated MIBG.

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“…Probably as little as four transport proteins account for accumulation of transmitter in synaptic vesicles: the acetylcholine transporter (Koeningsberger and Parsons, 1980), a GABA/glycine transporter (Fyske and Fonnum, 1988;Hell et al, 1988;Kish et al, 1989), a glutamate carrier (Disbrow et al, 1982;Naito and Ueda, 1983;Maycox et al, 1988) and a non-specific monoamine carrier (see Njus et al, 1986;Erickson et al, 1992;Liu et al, 1992). Large, dense-cored vesicles may only contain the monoamine carrier and contain peptides that they have received while budding from the Golgi apparatus.…”

Section: The Availability Of Transmitters For Releasementioning

confidence: 99%