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Direct modification of the 5-HT 3 receptor current by some anticancer drugs.

Authors :: Nakamura Y
Ishida Y
Kondo M
Shimada S
Source :: European journal of pharmacology [Eur J Pharmacol] 2018 Feb 15; Vol. 821, pp. 21-28. Date of Electronic Publication: 2017 Dec 22.
Publication Year :: 2018
Abstract: The serotonin (5-hydroxytryptamine) type 3 (5-HT <subscript>3</subscript> ) receptor is an important target in the control of emesis, and 5-HT <subscript>3</subscript> receptor antagonists are effective against the early phase chemotherapy evoked vomiting. We recently reported that the anticancer drugs irinotecan and topotecan directly modulate the 5-HT-mediated 5-HT <subscript>3</subscript> receptor current in vitro. In addition, the drug response depends on the 5-HT <subscript>3</subscript> subunit composition. Here, we explored the effects of 35 anticancer drugs on the 5-HT <subscript>3</subscript> receptor current. We microinjected Xenopus laevis oocytes with human 5-HT <subscript>3</subscript> A cRNA or a combination of human 5-HT <subscript>3</subscript> A and human 5-HT <subscript>3</subscript> B cRNA, and performed two-electrode voltage clamp recordings of 5-HT <subscript>3</subscript> A and 5-HT <subscript>3</subscript> AB receptor currents in the presence of each of the 35 drugs. Over 25% of the drugs we tested inhibited or potentiated the 5-HT <subscript>3</subscript> receptor current. The drugs that modulated the 5-HT <subscript>3</subscript> receptor current had molecular weights of approximately 500. These results implied that these anticancer drugs could affect 5-HT <subscript>3</subscript> receptor.<br /> (Copyright © 2017 Elsevier B.V. All rights reserved.)