Mechanisms of the trophic actions of bombesin on the pancreas.

Bombesin has both direct and indirect effects [mediated through release of cholecystokinin (CCK)] on pancreatic secretion. Polyamine biosynthesis, essential for DNA synthesis, is increased in the pancreas after CCK stimulation. The purpose of this study was to examine the trophic effects of bombesin and to determine whether the mechanism of bombesin-induced pancreatic growth is mediated through synthesis of polyamines. The time course of bombesin-stimulated polyamine biosynthesis was defined. Rats were studied in groups of six and received intraperitoneal (i.p.) injections every 8 h of either saline, bombesin (10 micrograms/kg), CR1409 (2.5 mg/kg) (a CCK-receptor antagonist), or both to define the effects on pancreatic growth and polyamine biosynthesis. Rats were killed at 14 days and the pancreas was excised, weighed, and analyzed for protein, RNA, and DNA content. We found that bombesin produced significant pancreatic hyperplasia (increased pancreatic weight, protein, and DNA content) after 14 days. CR1409 inhibited only bombesin-stimulated DNA content. Bombesin stimulated polyamine biosynthesis as early as 2 h after administration of bombesin, but CR1409 had no effect. The trophic actions of bombesin are both direct and indirect (mediated through CCK), and the direct effects of bombesin are mediated by polyamine biosynthesis.