Dose-related involvement of CCK in bombesin-induced pancreatic growth.
We examined the role of CCK in bombesin-induced pancreatic growth in rats using the CCK receptor antagonist L-364,718. Rats (155 +/- 1 g, 8-10 per group) received subcutaneous injections every 8 h for 5 days with bombesin (0.6, 1.7 and 5 nmol/kg) or bombesin in combination with L-364,718 (1 mg/kg). After 5 days the pancreas was removed and pancreatic weight, protein content, DNA, amylase and chymotrypsin contents were determined. Bombesin produced a significant increase (48-475%) of pancreatic weight, tissue contents of protein, DNA, amylase and chymotrypsinogen (F = 82, P less than 0.001). When a large dose of bombesin (5 nmol/kg) was combined with L-364,718 a significant inhibition (up to 70%) of all tissue parameters was observed (P less than 0.001). L-364,718 did not affect the growth response to a small dose of bombesin (0.6 nmol/kg). Plasma CCK levels 15 min after a single injection of bombesin (0.6, 1.7 and 5 nmol/kg) were significantly increased in response to the 5 nmol/kg dose (2.0 +/- 0.7 to 3.4 +/- 0.8 pM, F = 6.9, P less than 0.01). No increases of CCK plasma levels were found in response to the 0.6 and 1.7 nmol/kg doses of bombesin, corresponding to the lack of effects of L-364,718 on growth parameters at these doses. Measuring the time-course of CCK plasma levels after a single injection of 5 nmol/kg bombesin revealed an increase from basal values of 1.4 +/- 0.3 pM to maximal levels of 3.5 +/- 0.5 pM after 15 min (F = 7.1, P less than 0.001). Values returned to basal after 60 min. These results suggest that low doses of bombesin act directly at the acinar cell or through release of non-CCK growth factors whereas high doses of bombesin act in part through CCK release.
Liehr
R M
RM
Department of Medicine, Kansas University Medical Center, Kansas City.
Reidelberger
R D
RD
Rosewicz
S
S
Bussjaeger
L J
LJ
Solomon
T E
TE
D000681:Amylases / Q000378:metabolism; D000818:Animals; D001570:Benzodiazepinones / Q000008:administration & dosage / Q000494:pharmacology*; D001839:Bombesin / Q000008:administration & dosage / Q000494:pharmacology*; D002766:Cholecystokinin / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D002919:Chymotrypsinogen / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D020109:Devazepide; D004305:Dose-Response Relationship, Drug; D007279:Injections, Subcutaneous; D008297:Male; D010179:Pancreas / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors; D012844:Sincalide / Q000494:pharmacology
D001570:Benzodiazepinones; D011506:Proteins; D011949:Receptors, Cholecystokinin; D004247:DNA; D002766:Cholecystokinin; D002919:Chymotrypsinogen; D000681:Amylases; D020109:Devazepide; D012844:Sincalide; D001839:Bombesin