The antimalarial drug quinine interferes with serotonin biosynthesis and action

Farida Hanim Islahudin, Sarah M. Tindall, Ian R. Mellor, Karen Swift, Hans E M Christensen, Kevin C F Fone, Richard J. Pleass, Kang Nee Ting, Simon V. Avery

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish
Article number3618
JournalScientific Reports
Volume4
DOIs
Publication statusPublished - 9 Jan 2014

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Quinine
Antimalarials
Serotonin
Tryptophan
Tryptophan Hydroxylase
Essential Amino Acids
Serotonin Receptors
Neurotransmitter Agents
Yeasts

ASJC Scopus subject areas

  • General

Cite this

Islahudin, F. H., Tindall, S. M., Mellor, I. R., Swift, K., Christensen, H. E. M., Fone, K. C. F., ... Avery, S. V. (2014). The antimalarial drug quinine interferes with serotonin biosynthesis and action. Scientific Reports, 4, [3618]. https://doi.org/10.1038/srep03618

The antimalarial drug quinine interferes with serotonin biosynthesis and action. / Islahudin, Farida Hanim; Tindall, Sarah M.; Mellor, Ian R.; Swift, Karen; Christensen, Hans E M; Fone, Kevin C F; Pleass, Richard J.; Ting, Kang Nee; Avery, Simon V.

In: Scientific Reports, Vol. 4, 3618, 09.01.2014.

Research output: Contribution to journalArticle

Islahudin, FH, Tindall, SM, Mellor, IR, Swift, K, Christensen, HEM, Fone, KCF, Pleass, RJ, Ting, KN & Avery, SV 2014, 'The antimalarial drug quinine interferes with serotonin biosynthesis and action', Scientific Reports, vol. 4, 3618. https://doi.org/10.1038/srep03618
Islahudin, Farida Hanim ; Tindall, Sarah M. ; Mellor, Ian R. ; Swift, Karen ; Christensen, Hans E M ; Fone, Kevin C F ; Pleass, Richard J. ; Ting, Kang Nee ; Avery, Simon V. / The antimalarial drug quinine interferes with serotonin biosynthesis and action. In: Scientific Reports. 2014 ; Vol. 4.
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