TY - JOUR
T1 - Dose-dependent effect of chronic CR 1409 administration on rat exocrine pancreas in normal rats and following subtotal gastrectomy
AU - Glasbrenner, B.
AU - Malfertheiner, P.
AU - Bückler, M.
AU - Brändie, F.
AU - Friess, H.
AU - Ditschuneit, H.
PY - 1990/12
Y1 - 1990/12
N2 - Billroth II subtotal gastrectomy (B II) in rats results in pancreatic hyperplasia and hypertrophy, and affects pancreatic enzyme composition. A postulated mechanism for this effect is an increased postprandial release of endogenous CCK. In the present study, the influence of chronic administration of the CCK receptor antagonist CR 1409 was tested in B II and control rats. Forty male Wistar rats underwent B II subtotal gastrectomy and were divided into three groups. Group A: 20 rats with a standard diet; group B: 10 rats with low dose CR 1409 (0.3 mg/kg bw/d) in the diet; group C: 10 rats with high dose CR 1409 (3.0 mg/kg bw/d). Each rat of groups B and C was pair-fed with one animal of group A. Further, 40 control rats with no operation served as controls, and were, similarly to the B II rats, divided into three groups. After 28 d, the animals were sacrificed; wet wt, DNA-, protein-, amylase-, trypsin, and lipase content and concentration of the pancreas were determined. Basal CCK plasma levels were measured at the day of pancreatic explantation. Low dose CR 1409 induced an increase of pancreatic wet wt by 28%, and of DNA content by 26% in B II rats. High dose CR 1409 had no effect. Both doses of CR 1409 had similar effects on pancreatic enzyme concentrations (U/mg DNA); amylase increased by 50% in group B, and by 86% in group C, trypsin by 35% in group B, and by 41 % in group C; lipase was unchanged. In control rats, low dose CR 1409 induced pancreatic growth (wet wt + 27%; DNA content +24%) and enzyme adaptation (amylase +96%, trypsin +54%). High dose CR 1409 had no effect. Basal CCK plasma levels after an overnight fast were unaltered in all groups. In summary, low dose CR 1409 promotes pancreatic growth and affects enzyme composition in control rats. In B II rats, the trophic pancreatic response is further increased by low dose CR 1409. High dose CR 1409 had no effect in both experimental groups.
AB - Billroth II subtotal gastrectomy (B II) in rats results in pancreatic hyperplasia and hypertrophy, and affects pancreatic enzyme composition. A postulated mechanism for this effect is an increased postprandial release of endogenous CCK. In the present study, the influence of chronic administration of the CCK receptor antagonist CR 1409 was tested in B II and control rats. Forty male Wistar rats underwent B II subtotal gastrectomy and were divided into three groups. Group A: 20 rats with a standard diet; group B: 10 rats with low dose CR 1409 (0.3 mg/kg bw/d) in the diet; group C: 10 rats with high dose CR 1409 (3.0 mg/kg bw/d). Each rat of groups B and C was pair-fed with one animal of group A. Further, 40 control rats with no operation served as controls, and were, similarly to the B II rats, divided into three groups. After 28 d, the animals were sacrificed; wet wt, DNA-, protein-, amylase-, trypsin, and lipase content and concentration of the pancreas were determined. Basal CCK plasma levels were measured at the day of pancreatic explantation. Low dose CR 1409 induced an increase of pancreatic wet wt by 28%, and of DNA content by 26% in B II rats. High dose CR 1409 had no effect. Both doses of CR 1409 had similar effects on pancreatic enzyme concentrations (U/mg DNA); amylase increased by 50% in group B, and by 86% in group C, trypsin by 35% in group B, and by 41 % in group C; lipase was unchanged. In control rats, low dose CR 1409 induced pancreatic growth (wet wt + 27%; DNA content +24%) and enzyme adaptation (amylase +96%, trypsin +54%). High dose CR 1409 had no effect. Basal CCK plasma levels after an overnight fast were unaltered in all groups. In summary, low dose CR 1409 promotes pancreatic growth and affects enzyme composition in control rats. In B II rats, the trophic pancreatic response is further increased by low dose CR 1409. High dose CR 1409 had no effect in both experimental groups.
KW - B II subtotal gastrectomy
KW - CCK receptor antagonist
KW - pancreatic trophism
UR - http://www.scopus.com/inward/record.url?scp=0025546484&partnerID=8YFLogxK
U2 - 10.1007/BF02924454
DO - 10.1007/BF02924454
M3 - Article
AN - SCOPUS:0025546484
SN - 1537-3649
VL - 7
SP - 315
EP - 324
JO - International Journal of Pancreatology
JF - International Journal of Pancreatology
IS - 4
ER -