Capsaicin Is a Negative Allosteric Modulator of the 5-HT3 Receptor
Eslam El Nebrisi, Tatiana R. Prytkova, Dietrich E. Lorke, Luke Howarth, Asma Hassan Alzaabi, Keun‐Hang Susan Yang, Frank Christopher Howarth, Murat Öz
Abstract
In this study, the effects of capsaicin, an active ingredient of the capsicum plant, were investigated on human 5-hydroxytryptamine type 3 (5-HT3) receptors. Capsaicin reversibly inhibited serotonin (5-HT)-induced currents recorded by the two-electrode voltage-clamp method in Xenopus oocytes. The inhibition was time and concentration-dependent with an IC50 = 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 radioligand binding studies, capsaicin did not change the specific binding of the 5-HT3 antagonist [3H]GR65630, indicating that it is a noncompetitive inhibitor of the 5-HT3 receptor. In HEK-293 cells, capsaicin inhibited 5-HT3 receptor-induced aequorin luminescence with an IC50 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-HT3 receptors.