AUTHOR=Nebrisi Eslam El , Prytkova Tatiana , Lorke Dietrich Ernst , Howarth Luke , Alzaabi Asma Hassan , Yang Keun-Hang Susan , Howarth Frank C. , Oz Murat 

TITLE=Capsaicin Is a Negative Allosteric Modulator of the 5-HT3 Receptor

JOURNAL=Frontiers in Pharmacology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.01274

DOI=10.3389/fphar.2020.01274

ISSN=1663-9812

ABSTRACT=<p>In this study, effects of capsaicin, an active ingredient of the capsicum plant, were investigated on human 5-hydroxytryptamine type 3 (5-HT<sub>3</sub>) receptors. Capsaicin reversibly inhibited serotonin (5-HT)-induced currents recorded by two-electrode voltage clamp method in <italic>Xenopus</italic> oocytes. The inhibition was time- and concentration-dependent with an IC<sub>50</sub> = 62 μM. The effect of capsaicin was not altered in the presence of capsazepine, and by intracellular BAPTA injections or trans-membrane potential changes. In radio-ligand binding studies, capsaicin did not change the specific binding of the 5-HT<sub>3</sub> antagonist [<sup>3</sup>H]GR65630, indicating that it is a noncompetitive inhibitor of 5-HT<sub>3</sub> receptor. In HEK-293 cells, capsaicin inhibited 5-HT<sub>3</sub> receptor induced aequorin luminescence with an IC<sub>50</sub> of 54 µM and inhibition was not reversed by increasing concentrations of 5-HT. In conclusion, the results indicate that capsaicin acts as a negative allosteric modulator of human 5-HT<sub>3</sub> receptors.</p>