Vol. 63, Issue 5, 1067-1074, May 2003

Direct Interaction of Serotonin Type 3 Receptor Ligands with Recombinant and Native 910-Containing Nicotinic Cholinergic Receptors

Carla V. Rothlin, Maria I. Lioudyno, Ana F. Silbering, Paola V. Plazas, María E. Gomez Casati, Eleonora Katz, Paul S. Guth, and A. Belén Elgoyhen

Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad de Buenos Aires (C.V.R., A.F.S., P.V.P., M.E.G.C., E.K., A.B.E.), Departamento de Biología, Facultad de Científicas Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina (E.K.); and Department of Pharmacology, Tulane University, New Orleans, Louisiana (M.I.L., P.S.G.).

In the present work, we characterized the effects of serotonin type 3 receptor ligands on recombinant and native 910-containing nicotinic acetylcholine receptors (nAChRs). Our results indicate that the recombinant 910 nAChR shares striking pharmacological properties with 5-HT₃ ligand-gated ion channels. Thus, 5-HT₃ receptor antagonists block ACh-evoked currents in 910-injected Xenopus laevis oocytes with a rank order of potency of tropisetron (IC₅₀, 70.1 ± 0.9 nM) > ondansetron (IC₅₀, 0.6 ± 0.1 µM) = MDL 72222 (IC₅₀, 0.7 ± 0.1 µM). Although serotonin does not elicit responses in 910-injected oocytes, it blocks recombinant 910 receptors in a noncompetitive and voltage-dependent manner (IC₅₀, 5.4 ± 0.6 µM). On the other hand, we demonstrate an in vivo correlate of these properties of the recombinant receptor, with those of the 910-containing nAChR of frog saccular hair cells. The possibility that the biogenic amine serotonin might act as a neuromodulator of the cholinergic efferent transmission in the vestibular apparatus and in the organ of Corti is discussed.