Abstract
In the present study, we provide evidence that the α9 nicotinic acetylcholine receptor (nAChR) shares pharmacological properties with members of the Cys-loop family of receptors. Thus, the type A γ-aminobutyric acid receptor antagonist bicuculline, the glycinergic antagonist strychnine, and the type 3 serotonin receptor antagonist ICS-205,930 block ACh-evoked currents in α9-injected Xenopus laevis oocytes with the following rank order of potency: strychnine > ICS-205,930 > bicuculline. Block by antagonists was reflected in an increase in the acetylcholine (ACh) EC50 value, with no changes in agonist maximal response or Hill coefficient, which suggests a competitive type of block. Moreover, whereas neither γ-aminobutyric acid nor glycine modified ACh-evoked currents, serotonin blocked responses to ACh in a concentration-dependent manner. The present results suggest that the α9 nAChR must conserve in its primary structure some residues responsible for ligand binding common to other Cys-loop receptors. In addition, it adds further evidence that the α9 nAChR and the cholinergic receptor present at the base of cochlear outer hair cells have similar pharmacological properties.
Footnotes
- Received July 15, 1998.
- Accepted October 30, 1998.
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Send reprint requests to: Dr. A Belén Elgoyhen, Instituto de Investigaciones en Ingenierı́a Genética y Biologı́a, Molecular (CONICET-UBA), Obligado 2490, Buenos Aires 1428, Argentina. E-mail:elgoyhen{at}dna.uba.ar
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This work was supported by an International Research Scholar grant from the Howard Hughes Medical Institute, the Pew Charitable Trusts, the National Organization for Hearing Research (USA), and Fundación Antorchas (Argentina).
- The American Society for Pharmacology and Experimental Therapeutics
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