MECHANISM OF BOMBESIN-INDUCED PANCREATIC-SECRETION IN UNANESTHETIZED RATS

It is unclear whether stimulation of pancreatic enzyme secretion by in travenously administered bombesin is a direct effect on acinar cells o r is mediated by release of CCK; this distinction is important for def ining the potential role of bombesin-like peptides as regulators of pa ncreatic secretion. The role of CCK in bombesin-induced pancreatic sec retion was examined in rats using CCK radioimmunoassay and the CCK rec eptor antagonist L-364,718. A biphasic pancreatic response occurred to sequential doubling doses of bombesin (31 to 2000 pmol/kg/h, each for 30 min; n = 9 rats); amylase secretion increased to a peak at 250 pmo l/kg/h (11.5 +/- 1.7 kU/30 min; 4.2 +/- 0.6 kU/30 min, basal) and then declined to basal levels at 2000 pmol/kg/h. The ED50 dose of bombesin for stimulation was 31 pmol/kg/h, and the maximal response did not di ffer significantly from that to exogenous CCK-8 (10.6 +/- 1.5 kU/30 mi n) in the same rats. When single doses of bombesin were infused for 2 h (31, 62, 125, 250 pmol/kg/h; one dose per day; order randomized; n = 8), a similar dose-response relationship was seen, both for peak amyl ase response and cumulative output over basal. L-364,718 (0.5 mg/kg IV ) had no effect on the pancreatic response to ED50 or maximal doses of bombesin. Neither dose of bombesin altered plasma CCK levels. In cont rast, other stimulants of pancreatic secretion (food ingestion, soybea n trypsin inhibitor) caused marked elevations in plasma CCK levels. Th ese results indicate that the potent stimulation of pancreatic secreti on by exogenous bombesin in rats is not mediated by CCK, similar to fi ndings in humans.