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Release of amines from acidified stores following accumulation by Transport-P

Al-Damluji, S; Shen, WB; (2001) Release of amines from acidified stores following accumulation by Transport-P. British Journal of Pharmacology , 132 (4) pp. 851-860.

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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 degreesC but accelerated exponentially at higher temperatures up to 33 degreesC. The activation energy for the release of prazosin is 83.1 kJ mol(-1), corresponding to a temperature quotient (Q(10),) 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

Type: Article
Title: Release of amines from acidified stores following accumulation by Transport-P
Keywords: ACCUMULATION, Acidity, ACTIVATION, AGENT, AGENTS, antidepressant, Antidepressants, Antidepressive Agents, As, ATPase, Biological Transport, Boron Compounds, cell, Cell Line, CELL-LINE, Cells, Cultured, Chloroquine, Desipramine, Dose-Response Relationship, Drug, ENERGIES, energy, EQUATION, extracellular, extracellular pH, Fluorescence, functional, gradient, Hydrogen-Ion Concentration, Hypothalamus, IM, INHIBIT, intracellular, LA, LIGAND, ligands, LINE, LOCATION, MECHANISM, metabolism, Microscopy, Monensin, Neurones, Other, pH, pharmacology, PRAZOSIN, process, processes, Properties, Property, RANGE, release, RETENTION, sensitive, Structure, Temperature, uptake, vesicles, CELLS, DERIVATIVES, English, hormone, INHIBITOR, Ionophores, nature, NEUROTRANSMITTER TRANSPORTERS, NORADRENALINE, PEPTIDERGIC NEURONS, POSTSYNAPTIC NEURONS, Publishing, REQUIRES
UCL classification: UCL > School of Life and Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of)
URI: http://discovery.ucl.ac.uk/id/eprint/188235
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