PEPTIDE AMIDATING ACTIVITY AND GASTRIN PROCESSING IN THE DEVELOPING SHEEP PANCREAS

Gastrin is a regulator of both gastric acidity and gastrointestinal gr owth and is expressed transiently in the neonatal ovine and human panc reas. C-terminal amidation of glycine extended gastrin (G-gly) to gast rin amide (G-amide) by peptidylglycine alpha-amidating mono-oxygenase (PAM) is the final processing step. To investigate the relationship be tween PAM and gastrin synthesis in the developing pancreas, we measure d PAM activity and the concentrations of gastrins in ovine pancreatic extracts from 95 days of gestation onwards. Pancreatic PAM activity wa s highest in the 95-day-old fetus (138+/-129 pmol/h/mg protein, mean+/ -S.E.M.) and decreased to 9.5+/-3.7 pmol/h/mg protein in the adult. Th e circulating enzyme was also highest in the youngest fetus (1840+/-16 5 pmol/h/ml plasma) decreasing to approximately 50% in the 135-day-old fetus, with no further significant changes. The concentration of bioa ctive G-amide in the pancreas was 2.0+/-0.6 pmol/g at 95 days of gesta tion, 34+/-0.9 pmol/g at 135 days and decreased to 0.7+/-0.1 pmol/g in the adult. The precursor G-gly followed a similar pattern but its con centration was less than 10% of G-amide. These results show that: (a) there are high levels of PAM activity in the ovine fetal pancreas and in the fetal circulation, (b) PAM activity is apparently not rate-limi ting in the bioactivation of pancreatic gastrin and (c) the dual expre ssion of both PAM and gastrin in the fetal pancreas is similar to that observed in peptide-secreting tumours of the adult.