The effects of a somatostatin monoclonal antibody on gastrin and insulin release release_7otqqajh4zfvbkigzg6j6qssfu

Abstract

The effects of endogenous somatostatin on gastrin and insulin release were studied by passive immunization with a somatostatin monoclonal antibody, SOMA 10, in the isolated perfused rat stomach and pancreas, respectively. Previous passive immunization studies with somatostatin antiserum in the isolated perfused stomach have yielded conflicting results. The differences in results could be due to the differences in the binding characteristics of the antisera used, and the accessibility of the antiserum to the tissue. In previous studies in vivo and in isolated islets, somatostatin antiserum caused an increase in insulin release. Previous attempts at immunoneutralizing somatostatin in the isolated perfused pancreas of mammals have yielded negative results. However, the isolated perfused pancreas is an ideal model for passive immunization studies, because hormonal and central nervous system influences are eliminated, and the microanatomy of the islet is preserved. This study differed from previous studies in that a monoclonal antibody to somatostatin, which is more specific than somatostatin antiserum, was used in an attempt to neutralize endogenous gastric and pancreatic somatostatin. Fab fragments of SOMA 10 were made by papain digestion and purification on protein A-sepharose. These fragments are advantageous for passive immunization, since they contain the somatostatin binding site, and are much smaller than the intact antibody. Therefore they should more readily penetrate into the interstitium and neutralize endogenous somatostatin. SOMA 10 was purified by ammonium sulphate precipitation, in conjunction with hydroxylapatite chromatography. Purity was checked by gel filtration and affinity HPLC and determined to be 93%. Scatchard analysis calculated the binding capacity of SOMA 10 to be 8.3 μg/mg, and the dissociation constant to be 2.2 nM. Both SOMA 10 and the Fab fragments were shown to inhibit the effect of exogenously administered somatostatin in the isolated perfused stomach and in gastric fistula rats. Si [...]
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