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  The vesicular monoamine content regulates VMAT2 activity through Gq in mouse platelets

Höltje, M., Winter, S., Walther, D., Pahner, I., Hörtnagl, H., Ottersen, O. P., et al. (2003). The vesicular monoamine content regulates VMAT2 activity through Gq in mouse platelets. Journal of Biological Chemistry, 278(18), 15850-15858. doi:10.1074/jbc.M212816200.

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Genre: Zeitschriftenartikel
Alternativer Titel : J Biol Chem

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 Urheber:
Höltje, Markus, Autor
Winter, Sandra, Autor
Walther, Diego1, Autor
Pahner, Ingrid, Autor
Hörtnagl, Heide, Autor
Ottersen, Ole Peter, Autor
Bader, Michael, Autor
Ahnert-Hilger, Gudrun, Autor
Affiliations:
1Max Planck Society, ou_persistent13              

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 Zusammenfassung: Variations in the neurotransmitter content of secretory vesicles enable neurons to adapt to network changes. Vesicular content may be modulated by vesicle-associated Go2, which down-regulates the activity of the vesicular monoamine transmitter transporters VMAT1 in neuroendocrine cells and VMAT2 in neurons. Blood platelets resemble serotonergic neurons with respect to transmitter storage and release. In streptolysin O-permeabilized platelets, VMAT2 activity is also down-regulated by the G protein activator guanosine 5'-(i-imido)triphosphate (GMppNp). Using serotonin-depleted platelets from peripheral tryptophan hydroxylase knockout (Tph1/) mice, we show here that the vesicular filling initiates the G protein-mediated down-regulation of VMAT2 activity. GMppNp did not influence VMAT2 activity in naive platelets from Tph1/ mice. GMppNp-mediated inhibition could be reconstituted, however, when preloading Tph1/ platelets with serotonin or noradrenaline. Gq mediates the down-regulation of VMAT2 activity as revealed from uptake studies performed with platelets from Gq deletion mutants. Serotonergic, noradrenergic, as well as thromboxane A2 receptors are not directly involved in the down-regulation of VMAT2 activity. It is concluded that in platelets the vesicle itself regulates transmitter transporter activity via its content and vesicle-associated Gq.

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Sprache(n): eng - English
 Datum: 2003-05
 Publikationsstatus: Erschienen
 Seiten: -
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: -
 Identifikatoren: eDoc: 191983
DOI: 10.1074/jbc.M212816200
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Titel: Journal of Biological Chemistry
  Alternativer Titel : J Biol Chem
Genre der Quelle: Zeitschrift
 Urheber:
Affiliations:
Ort, Verlag, Ausgabe: -
Seiten: - Band / Heft: 278 (18) Artikelnummer: - Start- / Endseite: 15850 - 15858 Identifikator: ISSN: 0021-9258
ISSN: 1083-351X