ISOLATION OF VERTEBRATE NEURAL CHOLESCYSTOKININ HOMOLOGS

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Cholecystokinin (CCK) and gastrin are members of a family of neuralgastrointestinal peptides. CCK is one of the most abundant vertebrate brain peptides. However, no neural function(s) has been elucidated for CCK. Evidence suggests that CCK may be involved in learning, memory and the regulation of feeding. CCK is co-localized with classical transmitters, e.g., dopamine, and may function to regulate the release of classical transmitters. There is increasing evidence that unidentified CCK-related peptides exist in vertebrate neural tissue. A fundamental requirement to thoroughly understand the physiological roles of any neuropeptide family is to identify and characterize the primary structure of each peptide in that family. This proposal is designed to identify, isolate and characterize CCK-related peptides in vertebrate brain tissue. The immediate goals of this proposal include: 1) chromatographic separation and identification of CCK-related peptides in rat brain tissue using radioimmunoassays specific for CCK-like peptides, and 2) structural analyses of CCK-related peptides. Purification of CCK-related peptides will provide amino acid sequence data that can be used for further studies. Oligonucleotide probes can be designed to the peptides to isolate the DNA clones. Sequence-specific antibodies can be produced for localization studies. This information will provide the opportunity to address questions regarding regulation and expression of the CCK-related genes, precursor processing, site of peptide action within neural tissue and eventually, phenotypic and genotypic characteristics of the CCK-related peptides. Completion of these studies will provide the basis for studying the function of an important neuropeptide family at the molecular level. Future studies will utilize a multidisciplinary approach of biochemistry, histochemistry, molecular biology, neurobiology and physiology to investigate questions of regulation, function and expression. The proposed experiments will increase our understanding of a neuropeptide family involved in important physiological functions. When this important neuropeptide family is better understood, then perhaps researchers will be better able to understand learning, memory and eating-related disorders.