Direct interaction of serotonin type 3 receptor ligands with recombinant and native alpha 9 alpha 10-containing nicotinic cholinergic receptors.
In the present work, we characterized the effects of serotonin type 3 receptor ligands on recombinant and native alpha 9 alpha 10-containing nicotinic acetylcholine receptors (nAChRs). Our results indicate that the recombinant alpha 9 alpha 10 nAChR shares striking pharmacological properties with 5-HT(3) ligand-gated ion channels. Thus, 5-HT(3) receptor antagonists block ACh-evoked currents in alpha 9 alpha 10-injected Xenopus laevis oocytes with a rank order of potency of tropisetron (IC(50), 70.1 +/- 0.9 nM) > ondansetron (IC(50), 0.6 +/- 0.1 microM) = MDL 72222 (IC(50), 0.7 +/- 0.1 microM). Although serotonin does not elicit responses in alpha 9 alpha 10-injected oocytes, it blocks recombinant alpha 9 alpha 10 receptors in a noncompetitive and voltage-dependent manner (IC(50), 5.4 +/- 0.6 microM). On the other hand, we demonstrate an in vivo correlate of these properties of the recombinant receptor, with those of the alpha 9 alpha 10-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.
Rothlin
Carla V
CV
Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad de Buenos Aires, Argentina.
Lioudyno
Maria I
MI
Silbering
Ana F
AF
Plazas
Paola V
PV
Casati
María E Gomez
ME
Katz
Eleonora
E
Guth
Paul S
PS
Elgoyhen
A Belén
AB
D000818:Animals; D004594:Electrophysiology; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000502:physiology; D007211:Indoles / Q000494:pharmacology; D009865:Oocytes / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000235:genetics / Q000378:metabolism*; D044406:Receptors, Serotonin, 5-HT3; D011994:Recombinant Proteins / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology; D000077526:Tropisetron; D014982:Xenopus laevis
D007211:Indoles; D011978:Receptors, Nicotinic; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D011994:Recombinant Proteins; C443079:nAChR alpha9; C403531:nicotinic receptor alpha4beta2; D012701:Serotonin; D000077526:Tropisetron