Noncompetitive functional inhibition at diverse, human nicotinic acetylcholine receptor subtypes by bupropion, phencyclidine, and ibogaine

John D. Fryer, Ronald J. Lukas

Research output: Contribution to journalArticle

265 Scopus citations

Abstract

Nicotinic acetylcholine receptors (nAChR) are diverse members of the neurotransmitter-gated ion channel superfamily and play critical roles in chemical signaling throughout the nervous system. The present study establishes the acute functional effects of bupropion, phencyclidine, and ibogaine on two human nAChR subtypes. Function of muscle-type nAChR (α1βγδ) in TE671/RD cells or of ganglionic nAChR (α3β4α5±β2) in SH- SY5Y neuroblastoma cells was measured with 86Rb+ efflux assays. Functional blockade of human muscle-type and ganglionic nAChR is produced by each of the drugs in the low to intermediate micromolar range. Functional blockade is insurmountable by increasing agonist concentrations in TE671/RD and SH-SY5Y cells for each of these drugs, suggesting noncompetitive inhibition of nAChR function. Based on these findings, we hypothesize that nAChR are targets of diverse substances of abuse and agents used in antiaddiction/smoking cessation strategies. We also hypothesize that nAChR play heretofore underappreciated roles in depression and as targets for clinically useful antidepressants.

Original languageEnglish (US)
Pages (from-to)88-92
Number of pages5
JournalJournal of Pharmacology and Experimental Therapeutics
Volume288
Issue number1
StatePublished - Jan 1 1999

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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