Biosynthesis of Glucagon (IRG³⁵⁰⁰) in Canine Gastric Mucosa

The canine gastric mucosa has previously been shown to contain considerable amounts of a polypeptide with the immunologic and physicochemical characteristics and biologic activity of glucagon (IRG³⁵⁰⁰). Using mucosal pieces that remained viable for at least 8 h, we have demonstrated that IRG³⁵⁰⁰ is synthesized in this extrapancreatic tissue. Gel filtration and electrophoresis of extracts of mucosal pieces incubated with 3Htryptophan, ³H-leucine, or ³⁵S-methionine revealed small amounts of labeled, newly synthesized gastric IRG³⁵⁰⁰. No labeling of gastric IRG³⁵⁰⁰ was observed when the mucosa was incubated with ³H-proline, an amino acid not found in glucagon, in the presence of cycloheximide, or in isolated rat hepatocytes. Small amounts of newly synthesized IRG³⁵⁰⁰ were specifically immunoprecipitated by C-terminally directed glucagon antiserum gamma globulins. The rate of gastric IRG³⁵⁰⁰ biosynthesis in vitro was apparently unchanged in mucosal pieces from pancreatectomized dogs and unaffected by increased glucose or glucose lack during incubations. Thus we have provided evidence that a hormone of the endocrine pancreas can be synthesized in extrapancreatic tissues.