Nicotinic acetylcholine receptors and neurodegenerative disease.
Nicotinic acetylcholine receptor (nAChR) in the central nervous system represents a new potential therapeutic target in neurodegenerative diseases, and this is driven by new findings in the molecular biology of nicotinic ion channel. Results of epidemiological studies have revealed that the incidence of Alzheimer's disease is lower among smokers compared with findings for nonsmokers, which seems to indicate that nicotine may influence cortical functions. We observed an increase in extracellular dopamine concentrations after administration of nicotine through a microdialysis tube. Nicotine might inhibit the uptake of dopamine through the nAChR, which could serve as a preventive factor against neurodegenerative diseases. We evaluated the ability of nicotine to protect neuronal cells from death by using the model system of serum- and nerve growth factor (NGF)-free cultures of PC12 cells. Serum and NGF deprivation induced rapid and massive death of these cells, which was inhibited by the addition of nicotine. These results suggest to us that nicotine may be involved in the protection of neuronal cells from death by means of nAChR. The effect of NGF and nicotine on the expression of nAChR subunits in PC12 cells was examined by using Northern blot analysis. Nerve growth factor increased the transcription of alpha5 and beta4 subunits, whereas nicotine increased mRNA level encoding alpha5 and beta2 subunits. These results suggest to us that NGF changes the expression of nAChR in a subtype-specific manner over the course of differentiation, and disproportionate subunit expressions might be related to the neuroprotective effect exerted by nicotine.
Nakamura
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S
Third Department of Internal Medicine, Hiroshima University School of Medicine, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551, Japan. nakamura@mcai.med.hiroshima-u.ac.jp
Takahashi
T
T
Yamashita
H
H
Kawakami
H
H
D000818:Animals; D006801:Humans; D019636:Neurodegenerative Diseases / Q000503:physiopathology* / Q000517:prevention & control; D009538:Nicotine / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000502:physiology*
D011978:Receptors, Nicotinic; D009538:Nicotine