PARENTERALLY OR ENTERALLY ADMINISTERED ANTI-SOMATOSTATIN ANTIBODY INDUCES INCREASED GASTRIN IN SUCKLING RATS

Parenterally or enterally administered anti-somatostatin antibody indu ces increased gastrin in suckling rats. Am. J. Physiol. 266 (Gastroint est. Liver Physiol. 29): G417-G424, 1994. - This study demon strates t he effectiveness of parenteral and oral anti-somatostatin monoclonal a ntibody to stimulate gastrin cell activity in suckling rats. Intraperi toneal anti-somatostatin monoclonal antibody increased serum gastrin c oncentration (>2-fold), and orally administered antibodies retained th eir neutralizing capabilities as demonstrated by a 30% induction of ga strin synthesis. Absorption of luminal monoclonal antibody was time de pendent and saturable as demonstrated by measurement of serum murine i mmunoglobulin G and the subsequent effects on serum gastrin and antral gastrin mRNA concentrations. Enhanced gastrin synthesis after oral ad ministration required whole antibody in that enterally delivered F(ab' )(2) fragments were not absorbed and did not increase serum gastrin co ncentrations. In addition, pretreatment with excess Fe fragments decre ased monoclonal antibody absorption and eliminated the serum gastrin r esponse to oral monoclonal antibody. These results demonstrate that or ally administered murine anti-somatostatin monoclonal antibody was rap idly and efficiently absorbed via an Fc-dependent mechanism and retain ed immunoneutralizing activity against endogenous somatostatin, neutra lizing its inhibition of gastrin cell activity. These results indicate that orally administered monoclonal antibodies could potentially be u sed to determine the role of other peptides and growth factors as pote ntial physiological regulators during the suckling period of postnatal development.