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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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Item Permalink: https://hdl.handle.net/11858/00-001M-0000-0010-8A5E-D Version Permalink: https://hdl.handle.net/11858/00-001M-0000-0010-8A5F-B
Genre: Journal Article
Alternative Title : J Biol Chem

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

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 Abstract: 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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Language(s): eng - English
 Dates: 2003-05
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: eDoc: 191983
DOI: 10.1074/jbc.M212816200
 Degree: -

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Title: Journal of Biological Chemistry
  Alternative Title : J Biol Chem
Source Genre: Journal
 Creator(s):
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Publ. Info: -
Pages: - Volume / Issue: 278 (18) Sequence Number: - Start / End Page: 15850 - 15858 Identifier: ISSN: 0021-9258
ISSN: 1083-351X