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 with86Rb+ 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.
Footnotes
-
Send reprint requests to: Ronald J. Lukas, Division of Neurobiology, Barrow Neurological Institute, 350 W. Thomas Road, Phoenix, AZ 85013. E-mail:rlukas{at}mha.chw.edu
-
1 This work was supported by a grant from the Arizona Disease Control Research Commission (9730) and by faculty endowment and laboratory capitalization funds from the Men’s and Women’s Boards of the Barrow Neurological Foundation. The contents of this report are solely the responsibility of the authors and do not necessarily represent the views of the aforementioned rewarding agencies.
- Abbreviations:
- nAChR
- nicotinic acetylcholine receptors
- PCP
- phencyclidine
- carb
- carbamylcholine
- IC50
- concentration that inhibits response by 50%
- Received March 24, 1998.
- Accepted July 20, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
JPET 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.
|