PROPERTIES OF SOMATOSTATIN-LIKE IMMUNOREACTIVE POLYPEPTIDES IN THE CANINE EXTRAHYPOTHALAMIC BRAIN AND STOMACH

Polypeptides with somatostatin-like immunoreactivity (SLI) and approximate MW of 12,000, 3000 and 1600 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 [d] SLI was acidic, whereas the 3000 and 1600 d forms were basic molecules. All SLI fractions diluted proportionally in a radioimmunoassay employing an antibody directed toward the central region of somatostatin. Like synthetic somatostatin, the 1600 d SLI inhibited pentagastrin-stimulated gastric acid secretion in rats. Neither of the 2 larger forms of SLI were dissociated by 6 M guanidinium hydrochloride. Treatment with dithiothreitol, which reduces disulfide bonds, resulted in the conversion of a large portion of the 12,000 d SLI to the 1600 d form. These data apparently are compatible with a model of a 12,000-d SLI consisting of somatostatin bound to an acidic polypeptide by a peptide bond and a disulfide bond. Variations in the relative rates of hydrolysis of the peptide bonds and reduction of the disulfide bonds in different tissues may result in 3 forms of the 12,000 d polypeptide in which both bonds are intact or one of the 2 bonds is cleaved.