Somatostatin, a tetradecapeptide initially isolated from sheep hypothalami, has been described as having a wide range of actions in gastrointestinal tissues including a possible role as a neurotransmitter agent. The ubiquitous presence of somatostatin-like immunoreactivity (SLI) in gut tissues has been described by means of immunohistochemistry and radioimmunoassay techniques. I propose to study the physiologic significance of gut SLI by first describing its chemistry, and then studying mechanisms of its release as well as its potential role as a neurotransmitter. In preliminary studies, I have described two major molecular forms of human intestinal SLI; the smaller form (CMI) resembling hypothalamic somatostatin, and the other form (CMII) appearing as a larger and more basic peptide. I wish to further characterize SLI by isolation, analysis, and sequencing of these multiple forms. I will use the approach of reduction and carboxymethylation as a means of altering the chromatographic properties of CMI in order to isolate it for analysis. CMI will be isolated by means of affinity chromatography and high performance liquid chromatography. The release and synthesis of somatostatin from gastrointestinal tissues will be studied in increasingly more specific systems as follows: 1) measure the trophic effects of various peptides on gut SLI content, 2) study release of SLI from isolated perfused rat stomach and pancreas preparations and 2) measure release of SLI from enriched SLI containing cells from canine antral mucosa. The potential role of SLI as a neurotransmitter will be studied by first isolating and purifying it from gut muscle tissues, presumably of nerve origin, then studying its release and biosynthesis in retinal tissues, a system particularly adapted to this purpose.
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