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Updated: Aug 18, 2026
Localization of Plasma Membrane and Intracellular Neuronal Nicotinic Acetylcholine Receptors Using Quantitative Imaging in Mammalian Cells
Published on: December 19, 2025
Expression of the alpha7 nicotinic acetylcholine receptor in human lung cells
Howard K Plummer1, Madhu Dhar, Hildegard M Schuller
1Molecular Cancer Analysis Laboratory, Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996-4542, USA. hplummer@utk.edu
Background:
We and others have shown that one of the mechanisms of growth regulation of small cell lung cancer cell lines and cultured pulmonary neuroendocrine cells is by the binding of agonists to the alpha7 neuronal nicotinic acetylcholine receptor. In addition, we have shown that the nicotine-derived carcinogenic nitrosamine, 4(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), is a high affinity agonist for the alpha7 nicotinic acetylcholine receptor. In the present study, our goal was to determine the extent of alpha7 mRNA and protein expression in the human lung.
Methods:
Experiments were done using reverse transcription polymerase chain reaction (RT-PCR), a nuclease protection assay and western blotting using membrane proteins.
Results:
We detected mRNA for the neuronal nicotinic acetylcholine receptor alpha7 receptor in seven small cell lung cancer (SCLC) cell lines, in two pulmonary adenocarcinoma cell lines, in cultured normal human small airway epithelial cells (SAEC), one carcinoid cell line, three squamous cell lines and tissue samples from nine patients with various types of lung cancer. A nuclease protection assay showed prominent levels of alpha7 in the NCI-H82 SCLC cell line while alpha7 was not detected in SAEC, suggesting that alpha7 mRNA levels may be higher in SCLC compared to normal cells. Using a specific antibody to the alpha7 nicotinic receptor, protein expression of alpha7 was determined. All SCLC cell lines except NCI-H187 expressed protein for the alpha7 receptor. In the non-SCLC cells and normal cells that express the alpha7 nAChR mRNA, only in SAEC, A549 and NCI-H226 was expression of the alpha7 nicotinic receptor protein shown. When NCI-H69 SCLC cell line was exposed to 100 pm NNK, protein expression of the alpha7 receptor was increased at 60 and 150 min.
Conclusion:
Expression of mRNA for the neuronal nicotinic acetylcholine receptor alpha7 seems to be ubiquitously expressed in all human lung cancer cell lines tested (except for NCI-H441) as well as normal lung cells. The alpha7 nicotinic receptor protein is expressed in fewer cell lines, and the tobacco carcinogen NNK increases alpha7 nicotinic receptor protein levels.
Insights
The alpha7 nicotinic acetylcholine receptor (α7 nAChR) is present in human lung cancer cells and normal lung cells. The tobacco carcinogen NNK increases α7 nAChR protein levels in small cell lung cancer cells.
Area of Science:
- Oncology
- Neuroscience
- Pharmacology
Background:
- The alpha7 nicotinic acetylcholine receptor (α7 nAChR) plays a role in regulating the growth of small cell lung cancer (SCLC) and pulmonary neuroendocrine cells.
- The NNK carcinogen acts as a high-affinity agonist for the α7 nAChR.
Purpose of the Study:
- To investigate the expression of α7 nAChR mRNA and protein in human lung tissues and cancer cell lines.
- To determine the effect of NNK on α7 nAChR protein expression.
Main Methods:
- Reverse transcription polymerase chain reaction (RT-PCR) for mRNA detection.
- Nuclease protection assay for quantitative mRNA analysis.
- Western blotting for protein expression analysis.
Main Results:
- α7 nAChR mRNA was detected in various human lung cancer cell lines (SCLC, adenocarcinoma, carcinoid, squamous) and normal small airway epithelial cells (SAEC).
- α7 nAChR protein was expressed in most SCLC cell lines and some non-SCLC and normal lung cells.
- NNK exposure increased α7 nAChR protein levels in NCI-H69 SCLC cells.
Conclusions:
- α7 nAChR mRNA is widely expressed in human lung cancer and normal lung cells.
- α7 nAChR protein expression is more restricted, but present in key lung cancer subtypes.
- The tobacco carcinogen NNK can upregulate α7 nAChR protein expression, suggesting a potential mechanism for NNK-induced lung carcinogenesis.
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