Mechanism of bombesin-induced pancreatic secretion in unanesthetized rats.
It is unclear whether stimulation of pancreatic enzyme secretion by intravenously administered bombesin is a direct effect on acinar cells or is mediated by release of CCK; this distinction is important for defining the potential role of bombesin-like peptides as regulators of pancreatic secretion. The role of CCK in bombesin-induced pancreatic secretion was examined in rats using CCK radioimmunoassay and the CCK receptor 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 peak at 250 pmol/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 differ significantly from that to exogenous CCK-8 (10.6 +/- 1.5 kU/30 min) 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 amylase 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 contrast, other stimulants of pancreatic secretion (food ingestion, soybean trypsin inhibitor) caused marked elevations in plasma CCK levels. These results indicate that the potent stimulation of pancreatic secretion by exogenous bombesin in rats is not mediated by CCK, similar to findings in humans.
Liehr
R M
RM
Department of Gastroenterology, Free University Berlin, Germany.
Reidelberger
R D
RD
Varga
G
G
Solomon
T E
TE
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D001839:Bombesin / Q000494:pharmacology*; D002766:Cholecystokinin / Q000037:antagonists & inhibitors / Q000097:blood / Q000502:physiology*; D020109:Devazepide; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D008297:Male; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D001570:Benzodiazepinones; D002766:Cholecystokinin; D020109:Devazepide; D001839:Bombesin