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...
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| Format: | Article |
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Nature Publishing Group
2014
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| Online Access: | https://eprints.nottingham.ac.uk/40885/ |
| _version_ | 1848796155144568832 |
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| 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. |
| 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 |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| 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. |
| first_indexed | 2025-11-14T19:43:29Z |
| format | Article |
| id | nottingham-40885 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:43:29Z |
| publishDate | 2014 |
| publisher | Nature Publishing Group |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-408852020-05-04T16:41:58Z https://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 Islahudin, Farida, Tindall, Sarah M., Mellor, Ian R., Swift, Karen, Christensen, Hans E.M., Fone, Kevin C.F., 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 drug development enzyme mechanisms malaria mechanism of action http://www.nature.com/articles/srep03618 doi:10.1038/srep03618 doi:10.1038/srep03618 |
| spellingShingle | drug development enzyme mechanisms malaria mechanism of 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 antimalarial drug quinine interferes with serotonin biosynthesis and action |
| title | 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_short | The antimalarial drug quinine interferes with serotonin biosynthesis and action |
| title_sort | antimalarial drug quinine interferes with serotonin biosynthesis and action |
| topic | drug development enzyme mechanisms malaria mechanism of action |
| url | https://eprints.nottingham.ac.uk/40885/ https://eprints.nottingham.ac.uk/40885/ https://eprints.nottingham.ac.uk/40885/ |