Morantel allosterically enhances channel gating of neuronal nicotinic acetylcholine α3β2 receptors

Tse Yu Wu, Caleb M. Smith, Steven M Sine, Mark M. Levandoski

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

We studied allosteric potentiation of rat α3β2 neuronal nicotinic acetylcholine receptors (nAChRs) by the anthelmintic compound morantel. Macroscopic currents evoked by acetylcholine (ACh) from nAChRs expressed in Xenopus laevis oocytes increase up to 8-fold in the presence of low concentrations of morantel (≤10 μM); the magnitude of the potentiation depends on both agonist and modulator concentrations. It is noteworthy that the potentiated currents exceed the maximum currents achieved by saturating (millimolar) concentrations of agonist. Studies of macroscopic currents elicited by prolonged drug applications (100-300 s) indicate that morantel does not increase α3β2 receptor activity by reducing slow (≥1 s) desensitization. Instead, using outside-out patch-clamp recordings, we demonstrate that morantel increases the frequency of single-channel openings and alters the bursting characteristics of the openings in a manner consistent with enhanced channel gating; these results quantitatively explain the macroscopic current potentiation. Morantel is a very weak agonist alone, but we show that the classic competitive antagonist dihydro-β-erythroidine inhibits morantel-evoked currents noncompetitively, indicating that morantel does not bind to the canonical ACh binding sites.

Original languageEnglish (US)
Pages (from-to)466-475
Number of pages10
JournalMolecular Pharmacology
Volume74
Issue number2
DOIs
StatePublished - Aug 2008

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Morantel
Nicotinic Receptors
Acetylcholine
Anthelmintics
Xenopus laevis
Oocytes
Binding Sites

ASJC Scopus subject areas

  • Pharmacology

Cite this

Morantel allosterically enhances channel gating of neuronal nicotinic acetylcholine α3β2 receptors. / Wu, Tse Yu; Smith, Caleb M.; Sine, Steven M; Levandoski, Mark M.

In: Molecular Pharmacology, Vol. 74, No. 2, 08.2008, p. 466-475.

Research output: Contribution to journalArticle

Wu, Tse Yu ; Smith, Caleb M. ; Sine, Steven M ; Levandoski, Mark M. / Morantel allosterically enhances channel gating of neuronal nicotinic acetylcholine α3β2 receptors. In: Molecular Pharmacology. 2008 ; Vol. 74, No. 2. pp. 466-475.
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