Cholecystokinin (CCK) and gastrin are members of a family of neural-gastrointestinal peptides. CCK is one of the most abundant vertebrate brain peptides. The function(s) of CCK in nervous tissue is unknown. This proposal outlines studies of a CCK/gastrin homologue in the invertebrate, Drosophila. Genomic and cDNA clones have been isolated which contain two tandem DNA sequences, each with strong homology to CCK. Chromosomal localization maps the gene to the third chromosome. Preliminary in situ tissue localization indicates the presence of the transcript in the adult Drosophila head. The immediate goals of the proposal include: 1) complete genomic and cDNA sequence analyses, 2) isolation of naturally-occurring peptides and subsequent structural characterization, 3) identification of specific cells that express the gene by in situ hybridization, 4) generation of antibodies to synthetic peptides whose structures have been deduced from the DNA sequences and 5) construction of an anatomical map for the peptides by immunohistochemistry. DNA sequence analysis will provide information on possible control elements within the gene. Isolation of the naturally-occurring peptides will confirm processing sites, identify structure and demonstrate peptide existence. Structural data will be used to design synthetic peptides for future physiological studies. Localization data will suggest a function. This will provide information on regulation, processing and sites of action in Drosophila neural and gastrointestinal tissue.
