Document Detail


Tobacco particulate matter is more potent than nicotine at upregulating nicotinic receptors on SH-SY5Y cells.
MedLine Citation:
PMID:  17654292     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The effect of total particulate matter (TPM) from cigarette smoke on the expression and binding properties of nicotinic acetylcholine receptors (nAChRs) was investigated using a human neuroblastoma cell line (SH-SY5Y). TPM but not nicotine on its own inhibited cell growth at nicotine concentrations above 5 microM. To examine effects on nAChR expression, intact cells were incubated with 3H-epibatidine, and a Bmax of 13 fmoles/10(5) cells (7.8 x 10(4) binding sites/cell) was measured in unexposed cells as well as in cells treated with 2 microM nicotine alone or with TPM containing 2 microM nicotine. Using Scatchard analysis, we measured a Kd of 0.3 nM for 3H-epibatidine binding to nAChRs. This Kd was increased to 1.3 nM by addition of nicotine or TPM extract, both at 2 microM nicotine. Bmax, however, was unaffected, suggesting competitive binding of nicotine to its receptor. Short-term and prolonged 3-day exposures of SH-SY5Y cells to either TPM or nicotine at nicotine concentrations ranging from 0.2 microM to 20 microM increased specific binding, suggesting upregulation of nAChR expression. Most significant, binding was consistently greater in cells pretreated with TPM than in cells pretreated with nicotine. We conclude that TPM contains compounds that are toxic to cells at high concentrations (cell growth inhibition) but that do not compete with nicotine for binding to nAChRs (Scatchard analysis). These non-nicotinic compounds are capable of increasing the expression of one or more of the nAChR subunits. Furthermore, our cell culture assay provides a useful in vitro model for assessing the relative addictiveness of different tobacco products, including that of non-nicotine components.
Authors:
Vikki Ambrose; John H Miller; Stuart J Dickson; Scott Hampton; Penelope Truman; Rodney A Lea; Jefferson Fowles
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco     Volume:  9     ISSN:  1462-2203     ISO Abbreviation:  Nicotine Tob. Res.     Publication Date:  2007 Aug 
Date Detail:
Created Date:  2007-07-26     Completed Date:  2007-10-19     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9815751     Medline TA:  Nicotine Tob Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  793-9     Citation Subset:  IM    
Affiliation:
Institute of Environmental Science and Research Ltd., Porirua, New Zealand.
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MeSH Terms
Descriptor/Qualifier:
Binding Sites
Cell Line, Tumor
Cell Membrane / drug effects
Dose-Response Relationship, Drug
Humans
Membrane Potentials / drug effects
Neuroblastoma
Nicotine / pharmacology*
Nicotinic Agonists / pharmacology*
Patch-Clamp Techniques
Receptors, Nicotinic / drug effects*,  metabolism
Up-Regulation / drug effects*
Chemical
Reg. No./Substance:
0/Nicotinic Agonists; 0/Receptors, Nicotinic; 54-11-5/Nicotine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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