Polypeptides with somatostatin-like immunoreactivity (SLI) and approximate molecular weights of 12, 000, 3, 000, and 1, 600 were isolated from acid extracts of the canine extrahypothalamic brain and stomach by affinity chromatography, ion exchange, gel filtration, and isoelectric focusing. The 12, 000-dalton SLI was acidic, whereas the 3, 000- and 1, 600-dalton forms were basic molecules. All SLI fractions diluted proportionally in a RIA employing an antibody directed toward the central region of somatostatin. Like synthetic somatostatin, the 1, 600- dalton SLI inhibited pentagastrin-stimulated gastric acid secretion in rats. Neither of the two larger forms of SLI were dissociated by 6 M guanidinium HC1. However, treatment with dithiothreitol, which reduces disulfide bonds, resulted in the conversion of a large portion of the 12, 000-dalton SLI to the 1, 600- dalton form. These data are compatible with a model of a 12, 000- dalton SLI consisting of somatostatin bound to an acidic polypeptide by a peptide bond and a isulfide bond. Variations in the relative rates of hydrolysis of the peptide bonds and reductionof the disulfide bonds in different tissues may result in three forms of the 12, 000-dalton polypeptide in which both bonds are intact or one of the two bonds is cleaved.
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