Direct interaction of serotonin type 3 receptor ligands with recombinant and native alpha9alpha10-containing nicotinic cholinergic receptor

C.V. ROTHLIN; M.I. LIOUDYNO; A.F. SILBERING; P.V. PLAZAS; M.E. GOMEZ CASATI; E. KATZ; P.S. GUTH; A.B. ELGOYHEN

MOLECULAR PHARMACOLOGY

Año: 2003 vol. 63 p. 1067 - 1074

0026-895X

In the present work we perform an extensive characterization of the effects serotonin type 3 receptor ligands on recombinant and native a9a10-containing nicotinic cholinergic receptors. Our results indicate that the recombinant a9a10 nAChR shares striking properties with 5-HT3 ligand-gated ion channels. Thus, 5-HT3 receptor antagonists block ACh-evoked currents in a9a10-injected Xenopus laevis oocytes with a rank order of potency of tropisetron (IC50: 70.1 ± 0.9 nM) > ondansetron (IC50: 0.6 ± 0.1 mM) = MDL 72222 (IC50: 0.7 ± 0.1 mM). Whereas serotonin does not elicit responses in a9a10-injected oocytes, it blocks recombinant a9a10 receptors in a non-competitive and voltage-dependent manner (IC50 of 5.4 ± 0.6 mM). On the other hand, we demonstrate an in vivo correlate of these properties of the recombinant receptor, with those of the a9a10-containing nAChR of frog saccular hair cells. The possibility that the biogenic amine serotonin might act as a neuromodulator of the cholinergic efferent innervation to the vestibular apparatus and to the organ of Corti, is discussed.