The antimalarial drug quinine interferes with serotonin biosynthesis and action

The major antimalarial drug quinine perturbs uptake of the essential amino acid tryptophan, and patients with low plasma tryptophan are predisposed to adverse quinine reactions; symptoms of which are similar to indications of tryptophan depletion. As tryptophan is a precursor of the neurotransmitter...

Full description

Bibliographic Details
Main Authors:	Islahudin, Farida, Tindall, Sarah M., Mellor, Ian R., Swift, Karen, Christensen, Hans E.M., Fone, Kevin C.F., Pleass, Richard J., Avery, Simon V.
Format:	Article
Language:	English
Published:	Nature Publishing Group 2014
Online Access:	http://eprints.nottingham.ac.uk/40885/ http://eprints.nottingham.ac.uk/40885/ http://eprints.nottingham.ac.uk/40885/ http://eprints.nottingham.ac.uk/40885/1/Islahudin%20et%20al%20%282014%29%20Nature%20Sci.%20Rep.%20published%20pdf.pdf

id	nottingham-40885
recordtype	eprints
spelling	nottingham-408852017-10-12T22:20:26Z http://eprints.nottingham.ac.uk/40885/ The antimalarial drug quinine interferes with serotonin biosynthesis and action Islahudin, Farida Tindall, Sarah M. Mellor, Ian R. Swift, Karen Christensen, Hans E.M. Fone, Kevin C.F. Pleass, Richard J. Avery, Simon V. The major antimalarial drug quinine perturbs uptake of the essential amino acid tryptophan, and patients with low plasma tryptophan are predisposed to adverse quinine reactions; symptoms of which are similar to indications of tryptophan depletion. As tryptophan is a precursor of the neurotransmitter serotonin (5-HT), here we test the hypothesis that quinine disrupts serotonin function. Quinine inhibited serotonin-induced proliferation of yeast as well as human (SHSY5Y) cells. One possible cause of this effect is through inhibition of 5-HT receptor activation by quinine, as we observed here. Furthermore, cells exhibited marked decreases in serotonin production during incubation with quinine. By assaying activity and kinetics of the rate-limiting enzyme for serotonin biosynthesis, tryptophan hydroxylase (TPH2), we showed that quinine competitively inhibits TPH2 in the presence of the substrate tryptophan. The study shows that quinine disrupts both serotonin biosynthesis and function, giving important new insight to the action of quinine on mammalian cells. Nature Publishing Group 2014-01-09 Article PeerReviewed application/pdf en cc_by http://eprints.nottingham.ac.uk/40885/1/Islahudin%20et%20al%20%282014%29%20Nature%20Sci.%20Rep.%20published%20pdf.pdf Islahudin, Farida and Tindall, Sarah M. and Mellor, Ian R. and Swift, Karen and Christensen, Hans E.M. and Fone, Kevin C.F. and Pleass, Richard J. and Avery, Simon V. (2014) The antimalarial drug quinine interferes with serotonin biosynthesis and action. Scientific Reports, 4 (3618). pp. 1-7. ISSN 2045-2322 http://www.nature.com/articles/srep03618 doi:10.1038/srep03618 doi:10.1038/srep03618
repository_type	Digital Repository
institution_category	Local University
institution	University of Nottingham Malaysia Campus
building	Nottingham Research Data Repository
collection	Online Access
language	English
description	The major antimalarial drug quinine perturbs uptake of the essential amino acid tryptophan, and patients with low plasma tryptophan are predisposed to adverse quinine reactions; symptoms of which are similar to indications of tryptophan depletion. As tryptophan is a precursor of the neurotransmitter serotonin (5-HT), here we test the hypothesis that quinine disrupts serotonin function. Quinine inhibited serotonin-induced proliferation of yeast as well as human (SHSY5Y) cells. One possible cause of this effect is through inhibition of 5-HT receptor activation by quinine, as we observed here. Furthermore, cells exhibited marked decreases in serotonin production during incubation with quinine. By assaying activity and kinetics of the rate-limiting enzyme for serotonin biosynthesis, tryptophan hydroxylase (TPH2), we showed that quinine competitively inhibits TPH2 in the presence of the substrate tryptophan. The study shows that quinine disrupts both serotonin biosynthesis and function, giving important new insight to the action of quinine on mammalian cells.
format	Article
author	Islahudin, Farida Tindall, Sarah M. Mellor, Ian R. Swift, Karen Christensen, Hans E.M. Fone, Kevin C.F. Pleass, Richard J. Avery, Simon V.
spellingShingle	Islahudin, Farida Tindall, Sarah M. Mellor, Ian R. Swift, Karen Christensen, Hans E.M. Fone, Kevin C.F. Pleass, Richard J. Avery, Simon V. The antimalarial drug quinine interferes with serotonin biosynthesis and action
author_facet	Islahudin, Farida Tindall, Sarah M. Mellor, Ian R. Swift, Karen Christensen, Hans E.M. Fone, Kevin C.F. Pleass, Richard J. Avery, Simon V.
author_sort	Islahudin, Farida
title	The antimalarial drug quinine interferes with serotonin biosynthesis and action
title_short	The antimalarial drug quinine interferes with serotonin biosynthesis and action
title_full	The antimalarial drug quinine interferes with serotonin biosynthesis and action
title_fullStr	The antimalarial drug quinine interferes with serotonin biosynthesis and action
title_full_unstemmed	The antimalarial drug quinine interferes with serotonin biosynthesis and action
title_sort	antimalarial drug quinine interferes with serotonin biosynthesis and action
publisher	Nature Publishing Group
publishDate	2014
url	http://eprints.nottingham.ac.uk/40885/ http://eprints.nottingham.ac.uk/40885/ http://eprints.nottingham.ac.uk/40885/ http://eprints.nottingham.ac.uk/40885/1/Islahudin%20et%20al%20%282014%29%20Nature%20Sci.%20Rep.%20published%20pdf.pdf
first_indexed	2018-09-06T13:09:24Z
last_indexed	2018-09-06T13:09:24Z
_version_	1610863727981101056

The antimalarial drug quinine interferes with serotonin biosynthesis and action

Similar Items