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11181426

Source:http://linkedlifedata.com/resource/pubmed/id/11181426

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pubmed-article:11181426pubmed:abstractText1. Transport-P is an uptake process for amines in peptidergic neurones of the hypothalamus. It differs from other uptake processes by its anatomical location in post-synaptic neurones, its functional properties and by the structure of its ligands. Transport-P accumulates amines in intracellular vesicles, derives its energy from the electrochemical proton gradient and is linked to vacuolar-type ATPase (V-ATPase). Transport-P is blocked by antidepressants. We have now studied the release of amines following uptake by Transport-P in a cell line of hypothalamic peptidergic neurones. 2. Release of prazosin was not inhibited by the antidepressant desipramine; as Transport-P is blocked by desipramine, this indicated that amines are released by a mechanism which is independent of Transport-P. 3. Release of prazosin was sensitive to temperature and conformed to the Arrhenius equation. Release was minimal in the range 0-25 degrees C but accelerated exponentially at higher temperatures up to 33 degrees C. The activation energy for the release of prazosin is 83.1 kJ x mol(-1), corresponding to a temperature quotient (Q10) value of 3. 4. Release was accelerated by the organic base chloroquine, the ionophore monensin, bafilomycinA1 which inhibits V-ATPase and by increasing extracellular pH. Thus, retention of prazosin requires an intracellular proton gradient which is generated by V-ATPase. 5. Fluorescence microscopy demonstrated that release of BODIPY FL prazosin was temperature dependent and was accelerated by chloroquine and monensin. 6. Thus, following uptake by Transport-P, amines are accumulated in acidified intracellular stores. Their retention in peptidergic neurones requires intracellular acidity. The amines are released by a temperature-dependent process which is resistant to antidepressants.lld:pubmed
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pubmed-article:11181426pubmed:authorpubmed-author:Al-DamlujiSSlld:pubmed
pubmed-article:11181426pubmed:authorpubmed-author:ShenW BWBlld:pubmed
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pubmed-article:11181426pubmed:dateRevised2009-11-18lld:pubmed
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pubmed-article:11181426pubmed:articleTitleRelease of amines from acidified stores following accumulation by Transport-P.lld:pubmed
pubmed-article:11181426pubmed:affiliationDivision of Endocrinology, Royal Free and University College Medical School, University College London, London NW3 2PF. damluji@rfhsm.ac.uklld:pubmed
pubmed-article:11181426pubmed:publicationTypeJournal Articlelld:pubmed