Elsevier

Biochemical Pharmacology

Volume 59, Issue 3, 1 February 2000, Pages 233-240
Biochemical Pharmacology

Molecular and Cellular Pharmacology
Individual variation in the expression profiles of nicotinic receptors in the olfactory bulb and trigeminal ganglion and identification of α2, α6, α9, and β3 transcripts

https://doi.org/10.1016/S0006-2952(99)00326-3Get rights and content

Abstract

Nicotine evokes dose-dependent and often variable chemosensory responses in animals and humans. Earlier observations that nicotine binds to some nicotinic acetylcholine receptor (nAChR) subtypes in the olfactory bulb (OB) and trigeminal ganglion (TG) led us to investigate the complete nAChR expression profile in each tissue and to determine whether inter-individual differences exist in male and female rats. Total RNA was extracted from individual samples of dissected OB and TG and analyzed by a sensitive reverse transcription–polymerase chain reaction (RT–PCR) assay to determine the messenger RNA profiles of ten transcripts encoded by the α2, α3, α4, α5, α6, α7, α9, β2, β3, and β4 nAChR genes. We found that (a) in the OB, all animals expressed α2, α3, α4, α5, α7, β2, and β4 subunit mRNAs, whereas α6, β3, and α9 transcripts were expressed in only 17, 28, and 33% of the animals, respectively, and (b) in the TG, all animals expressed α2, α3, α6, α7, β2, and β4 subunit mRNAs, whereas α9, β3, α4, and α5 transcripts were expressed in 4, 38, 88, and 92% of the animals, respectively. These results also identified new subunits that are expressed in each tissue (α2, α6, α9, and β3) and demonstrated that individual rats may have different tissue-specific expression profiles for α4, α5, α6, α9, and β3 transcripts. Such variations are likely to be reflected in the composition of functional receptor subtypes in the rat OB and TG that have different activation and desensitization characteristics to acetylcholine and nicotine.

Section snippets

Animals and tissue collection

Naive adult Sprague–Dawley rats (200–400 g, Virus Antibody Free/Plus, Charles River Laboratories) were used in this study. The animals were housed individually in polycarbonate cages in a vivarium with controlled lighting (12 hr light/12 hr dark) and had ad lib. access to food and water. The temperature and relative humidity were maintained at 20–24° and 40–60%, respectively. Rats were anesthetized deeply with 70% CO2 and then decapitated. After the brain was removed from the skull, the OB and

Multiple neuronal nicotinic receptor subunit mRNAs are expressed in the OB and TG

Analysis of nAChR gene expression in the OB and TG showed individual variation and tissue-specific differences. In the OB, all animals expressed α2, α3, α4, α5, α7, β2, and β4 mRNAs in comparison with 17, 28, and 33% of the animals expressing α6, β3, and α9 mRNAs, respectively. More specifically, one male and two female rats expressed detectable levels of α6 mRNA. The same male rat also expressed a low level of α9 mRNA [see Fig. 1 (top panel) and Table 2].

Several variations in nAChR expression

Discussion

The new information we report here shows that nAChR gene expression varies among individual rats as well as from the OB to the TG. To our knowledge, no study of this nature has been done in sensory tissue of the rat or human despite the general importance of normative tissue differences as well as the need to better understand why some individuals have a greater degree of chemosensitivity to endogenous ACh or nicotine from tobacco products. Although the range for individual chemosensory

Acknowledgements

We thank Sheri Bowman and Walden Hearn for excellent technical assistance and Elyse Jung for DNA sequencing assistance. This project was supported by the UNC-RJR Collaborative Olfactory Research Program.

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    §

    Present address of Dr. James C. Walker: FSU-Sensory Research Institute, 1800 E. Paul Dr., Tallahassee, FL 32306-2741.

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