Abstract
In the present work, we characterized the effects of serotonin type 3 receptor ligands on recombinant and native α9α10-containing nicotinic acetylcholine receptors (nAChRs). Our results indicate that the recombinant α9α10 nAChR shares striking pharmacological properties with 5-HT3 ligand-gated ion channels. Thus, 5-HT3 receptor antagonists block ACh-evoked currents in α9α10-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 α9α10-injected oocytes, it blocks recombinant α9α10 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 α9α10-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.
Footnotes
-
↵1 A pithed frog has had its central nervous system destroyed (its spinal cord has been severed). It is dead, but some of its organs continue to function for a brief period.
-
This work was supported by an International Research Scholar grant from the Howard Hughes Medical Institute, the Beca Ramón Carrillo-Arturo Oñativia, the Agencia Nacional de Promoción Cientı́fica y Tecnológica (to A.B.E.), and National Institutes of Health grant DC00303 (to P.S.G). C.V.R and P.V.P. are supported by a Consejo Nacional de Investigaciones Cientı́ficas y Técnicas predoctoral fellowship, M.E.G.C. by a fellowship from ANPCyT, and A.F.S. by a Fundación Antorchas fellowship for undergraduates.
- Abbreviations:
- nAChR
- nicotinic acetylcholine receptor
- ACh
- acetylcholine
- 5-HT
- 5-hydroxytryptamine
- BAPTA-AM
- 1,2-bis(O-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid
- MDL 72222
- 3-tropanyl-3,5-dichlorobenzoate
- I-V
- current-voltage
- 5HTQ
- trimethyl serotonin
- ICS 205,930
- tropisetron
- Received August 5, 2002.
- Accepted January 24, 2002.
- The American Society for Pharmacology and Experimental Therapeutics
MolPharm articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|