The antimalarial drug quinine interferes with serotonin biosynthesis and action

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

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Abstract

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.

Item Type: Article
Keywords: drug development, enzyme mechanisms, malaria, mechanism of action
Schools/Departments: University of Nottingham, Malaysia > Faculty of Science > Department of Biomedical Sciences
University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Life Sciences
University of Nottingham, UK > Faculty of Science > School of Pharmacy
Identification Number: 10.1038/srep03618
Depositing User: Eprints, Support
Date Deposited: 27 Feb 2017 15:21
Last Modified: 01 Mar 2017 06:17
URI: http://eprints.nottingham.ac.uk/id/eprint/40885

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