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The antimalarial drug quinine interferes with serotonin biosynthesis and action.

Authors :
Islahudin F
Tindall SM
Mellor IR
Swift K
Christensen HE
Fone KC
Pleass RJ
Ting KN
Avery SV
Source :
Scientific reports [Sci Rep] 2014 Jan 09; Vol. 4, pp. 3618. Date of Electronic Publication: 2014 Jan 09.
Publication Year :
2014

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.

Details

Language :
English
ISSN :
2045-2322
Volume :
4
Database :
MEDLINE
Journal :
Scientific reports
Publication Type :
Academic Journal
Accession number :
24402577
Full Text :
https://doi.org/10.1038/srep03618