A central problem in biology in general, and neurobiology in particular, concerns the basic mechanisms by which cells communicate. Intercellular communication in the nervous system depends upon cell-specific elaboration of neurotransmitters and neurotransmitter receptors. The long- term goal of this project is to elucidate mechanisms by which neurons express appropriate postsynaptic receptors, resulting in a functional presynaptic-postsynaptic match. Preliminary experiments indicate that the rat liver beta- adrenergic receptor can be used as a model system to approach mechanisms governing cell-specific expression of neuronal receptors.
Specific aims of the proposed research include: 1) Identification, characterization and purification of the factors mediating density-dependent regulation of expression of beta-adrenergic receptors during culture of adult rat hepatocytes. 2) Determining whether the factors regulating expression of hepatic beta-receptors in cell culture regulate expression of receptors in vivo. 3) Determining whether the factors regulating expression of hepatic beta-adrenergic receptors are tissue specific. 4) Utilization of cDNA probes for beta-adrenergic receptor messenger RNA to determine the loci where expression of beta- adrenergic receptors is regulated both in vivo and during cell culture. 5) Defining the factors that regulate expression of neuronal beta-adrenergic receptors by utilizing regional brain cultures. The elucidation of mechanisms that regulate cell-specific expression of receptors is likely to lead to a better understanding of both normal and abnormal nervous system development. Ultimately, the identification and characterization of factors that regulate cell-specific expression of receptors might lead to additional therapeutic agents useful in the treatment of neurological disease.
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