Parenterally or enterally administered anti-somatostatin antibody induces increased gastrin in suckling rats.
This study demonstrates the effectiveness of parenteral and oral anti-somatostatin monoclonal antibody to stimulate gastrin cell activity in suckling rats. Intraperitoneal anti-somatostatin monoclonal antibody increased serum gastrin concentration (> 2-fold), and orally administered antibodies retained their neutralizing capabilities as demonstrated by a 30% induction of gastrin synthesis. Absorption of luminal monoclonal antibody was time dependent and saturable as demonstrated by measurement of serum murine immunoglobulin G and the subsequent effects on serum gastrin and antral gastrin mRNA concentrations. Enhanced gastrin synthesis after oral administration required whole antibody in that enterally delivered F(ab')2 fragments were not absorbed and did not increase serum gastrin concentrations. In addition, pretreatment with excess Fc fragments decreased monoclonal antibody absorption and eliminated the serum gastrin response to oral monoclonal antibody. These results demonstrate that orally administered murine anti-somatostatin monoclonal antibody was rapidly and efficiently absorbed via an Fc-dependent mechanism and retained immunoneutralizing activity against endogenous somatostatin, neutralizing its inhibition of gastrin cell activity. These results indicate that orally administered monoclonal antibodies could potentially be used to determine the role of other peptides and growth factors as potential physiological regulators during the suckling period of postnatal development.
Martín
M G
MG
Department of Pediatrics, University of California School of Medicine, Los Angeles 90024.
Wu
S V
SV
Ohning
G
G
Wong
H
H
Walsh
J H
JH
D000284:Administration, Oral; D000818:Animals; D000833:Animals, Suckling; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000494:pharmacology; D001483:Base Sequence; D001692:Biological Transport; D004305:Dose-Response Relationship, Drug; D005755:Gastrins / Q000235:genetics / Q000378:metabolism*; D007141:Immunoglobulin Fc Fragments / Q000494:pharmacology; D007074:Immunoglobulin G / Q000378:metabolism; D007263:Infusions, Parenteral; D007408:Intestinal Absorption / Q000187:drug effects; D007422:Intestines; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes / Q000235:genetics; D011706:Pyloric Antrum / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013004:Somatostatin / Q000276:immunology*
D000911:Antibodies, Monoclonal; D005755:Gastrins; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D013004:Somatostatin