Vesicular monoamine transporter 2

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VMAT2
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SLC18A2
Identifiers
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Ensembl
UniProt
RefSeq (mRNA)

NM_003054

NM_172523

RefSeq (protein)

NP_003045

NP_766111

Location (UCSC)Chr 10: 117.24 – 117.28 MbChr 19: 59.25 – 59.28 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse
Distribution of VMAT2 in the human brain.

The solute carrier family 18 member 2 (SLC18A2) also known as vesicular monoamine transporter 2 (VMAT2) is a

GABA.[7]

Binding sites and ligands

SLC18A2 is believed to possess at least two distinct binding sites, which are characterized by

membrane transport proteins for monoamines (i.e., the dopamine transporter, norepinephrine transporter, and serotonin transporter) in monoamine neurons. Other SLC18A2 inhibitors such as GZ-793A inhibit the reinforcing effects of methamphetamine, but without producing stimulant or reinforcing effects themselves.[9]

Researchers have found that inhibiting the dopamine transporter (but not SLC18A2) will block the effects of amphetamine and cocaine; while, in another experiment, observing that disabling SLC18A2 (but not the dopamine transporter) prevents any notable action in test animals after amphetamine administration yet not cocaine administration. This suggests that amphetamine may be an atypical substrate with little to no ability to prevent dopamine reuptake via binding to the dopamine transporter but, instead, uses it to enter a neuron where it then interacts with SLC18A2 to induce efflux of dopamine from their vesicles into the cytoplasm whereupon dopamine transporters with amphetamine substrates attached move this recently liberated dopamine into the synaptic cleft.[10]

Inhibition

SLC18A2 is essential for enabling the release of neurotransmitters from the axon terminals of monoamine neurons into the synaptic cleft. If SLC18A2 function is inhibited or compromised, monoamine neurotransmitters such as dopamine cannot be released into the synapse via typical release mechanisms (i.e., exocytosis resulting from action potentials).

neuronal changes could play a role in causing disordered mood and motivational processes in more severely addicted users.[11]

In popular culture

Geneticist Dean Hamer has suggested that a particular allele of the SLC18A2 gene correlates with spirituality using data from a smoking survey, which included questions intended to measure "self-transcendence". Hamer performed the spirituality study on the side, independently of the National Cancer Institute smoking study. His findings were published in the mass-market book The God Gene: How Faith Is Hard-Wired into Our Genes.[12][13] Hamer himself notes that SLC18A2 plays at most a minor role in influencing spirituality.[14] Furthermore, Hamer's claim that the SLC18A2 gene contributes to spirituality is controversial.[14] Hamer's study has not been published in a peer-reviewed journal and a reanalysis of the correlation demonstrates that it is not statistically significant.[14][15]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000165646 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000025094 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. S2CID 8062412
    .
  6. .
  7. .
  8. ^ . They also demonstrated competition for binding between METH and reserpine, suggesting they might bind to the same site on VMAT. George Uhl's laboratory similarly reported that AMPH displaced the VMAT2 blocker tetrabenazine (Gonzalez et al., 1994). Tetrabenazine and reserpine are thought to bind to different sites on VMAT (Schuldiner et al., 1993a)
  9. .
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  11. .
  12. .
  13. ^ Kluger J, Chu J, Liston B, Sieger M, Williams D (25 October 2004). "Is God in our genes?". TIME. Time Inc. Archived from the original on 30 September 2007. Retrieved 8 April 2007.
  14. ^
    PMID 18316816
    .
  15. .

Further reading

External links

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