title: The antimalarial drug quinine interferes with serotonin biosynthesis and action.
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.
authors.affiliation: 1] School of Life Sciences, University of Nottingham, Nottingham NG7 2RD, UK [2] School of Pharmacy, University of Nottingham Malaysia Campus, 43500 Semenyih, Malaysia [3].
authors.forename: Farida
authors.initials: F
authors.lastname: Islahudin
authors.affiliation: School of Life Sciences, University of Nottingham, Nottingham NG7 2RD, UK.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Tindall
authors.affiliation: School of Life Sciences, University of Nottingham, Nottingham NG7 2RD, UK.
authors.forename: Ian R
authors.initials: IR
authors.lastname: Mellor
authors.affiliation: School of Life Sciences, University of Nottingham, Nottingham NG7 2RD, UK.
authors.forename: Karen
authors.initials: K
authors.lastname: Swift
authors.affiliation: Department of Chemistry, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark.
authors.forename: Hans E M
authors.initials: HE
authors.lastname: Christensen
authors.affiliation: School of Life Sciences, University of Nottingham, Nottingham NG7 2RD, UK.
authors.forename: Kevin C F
authors.initials: KC
authors.lastname: Fone
authors.affiliation: University of Liverpool, Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Pleass
authors.affiliation: School of Life Sciences, University of Nottingham Malaysia Campus, 43500 Semenyih, Malaysia.
authors.forename: Kang-Nee
authors.initials: KN
authors.lastname: Ting
authors.affiliation: School of Life Sciences, University of Nottingham, Nottingham NG7 2RD, UK.
authors.forename: Simon V
authors.initials: SV
authors.lastname: Avery
mesh_terms: D000962:Antimalarials / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D009447:Neuroblastoma / Q000473:pathology; D011803:Quinine / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000254:growth & development; D012701:Serotonin / Q000096:biosynthesis* / Q000502:physiology; D014365:Tryptophan Hydroxylase / Q000037:antagonists & inhibitors
chemical_list: D000962:Antimalarials; D012701:Serotonin; D011803:Quinine; D014365:Tryptophan Hydroxylase