Effect of a synthetic analogue of PGE2 on exocrine and endocrine pancreatic function in the rat.

The effect of 16,16-dimethyl PGE2-methyl-ester (di-M-PGE2, a long-acting synthetic analogue of PGE2) on exocrine and endocrine pancreatic secretion was studied in rats with chronic pancreatic fistulas. Under basal conditions as well as after stimulation with secretin and OP-CCK, pancreatic exocrine secretion was inhibited markedly by intravenous injection of di-M-PGE2 at 10 microgram/kg and 100 microgram/kg. Secretory volumes and bicarbonate and protein outputs decreased within 10 minutes after the administration of di-M-PGE2, and this inhibitory effect persisted throughout the following 40 minutes. The smaller dose of di-M-PGE2 (10 microgram/kg) inhibited the volume of pancreatic secretion by an average of 47.7% and decreased bicarbonate and protein output by 41.1% and 70.5%, respectively. The larger dose (100 microgram/kg) caused a mean 48.3% inhibition of pancreatic secretory volume and decreased bicarbonate and protein outputs by 41.7% and 64.5%, respectively. Plasma insulin levels were lowered markedly after injection of di-M-PGE2 under basal conditions (mean inhibition 63.1% by PG-10 and 55.3% by PG-100) as well as after secretin stimulation (mean inhibition 89.5% by PG-10 and 82.4% by PG-100). These observations document that di-M-PGE2 is a potent inhibitor of pancreatic exocrine and endocrine function in the unanesthetized rat. In these actions the PGE2-analogue antagonized the stimulatory effects of both secretin and OP-CCK.