• Morley, Barbara J (PI)

    Project: Research project

    Project Details


    Eighty percent of smokers who quit relapse within a year. Although there
    are many reasons for relapse, the active ingredient in cigarettes,
    nicotine, has properties of an addictive substance. All of the actions of
    nicotine are not known, but nicotine is known to act as receptor sites in
    nervous tissues. Its action at acetylcholine receptor sites may be related
    to its addictive properties. The nicotinic acetylcholine receptors in mammalian brain have not been
    well-characterized. Nicotine binds with high affinity (Kd 1-10 nM) to at
    least one population of brain nicotinic receptors. The high-affinity
    binding to brain tissue is a paradox. Electrophysiological studies suggest
    that micromolar concentrations of nicotine are necessary for receptor
    activation. It has been suggested that the brain receptors are desensitized
    during the assay procedure (in which 10-20 nM concentrations of nicotine
    are used), indicating a 1000-fold difference between the K-activation (K-
    act) and K-desensitization (K-des) of nicotinic receptors in mammalian
    brain. Previous work in our laboratory indicates that the K-act and K-des of PC12
    cells, which possess a well-characterized neuronal receptor, are 7.7 X
    10(5) M and 8.2 X 10(5) M, respectively. On the basis of these data, we
    question whether the K-des and K-act in brain tissue would differ by 3
    orders of magnitude. This question cannot be resolved using brain tissue
    in vivo. We therefore propose to study this question in primary neuronal
    brain cultures using 22Na+ influx. 22Na+ influx has not previously been demonstrated in primary neuronal
    cultures derived from mammalian brain. Therefore, the goal of this research
    is to demonstrate nicotinic receptor mediated 22Na" influx in mammalian
    brain culture. Experiments using 22Na+ influx and nicotine and cytisine as
    agonists will be performed to determine the K-act and K-des of the
    receptors. Influx will be also carried out in the presence of nicotinic
    antagonists. These experiments will serve as the basis for future inves-
    tigations of the physiological properties of brain nicotinic receptors.
    Effective start/end date3/1/9110/31/93


    • National Institutes of Health: $71,600.00


    • Medicine(all)


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