Dose-related involvement of CCK in bombesin-induced pancreatic growth

Abstract

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 < 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 < 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 < 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 < 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.