The effects of graded doses of a cholecystokinin-like peptide with and without secretin on pancreatic growth and synthesis of RNA and polyamines in rats.
The dose dependence of a cholecystokinin-like peptide (CCK-LP) on the trophic response in the rat pancreas was studied. Graded doses of Thr28Nle31CCK25-33 (0.02, 0.1, 0.5, 2.5, and 12.5 micrograms/kg/h) or saline were given as a continuous intravenous infusion to conscious and fed rats for 8 and 48 h. Secretin (5.0 micrograms/h) was given alone or combined with the three highest doses of CCK-LP for 48 h. CCK-LP showed a dose-dependent stimulating effect on pancreatic growth and synthesis of RNA and polyamines. The threshold dose ranged from 0.02 to 0.5 micrograms/kg/h and was lowest for stimulation of ornithine decarboxylase (ODC). The maximal effects on protein, RNA, and DNA contents were achieved with 2.5 micrograms/kg/h. These same variables markedly decreased with 12.5 micrograms/kg/h, whereas marked further increases were found for the activities of RNA polymerase, DNA polymerase, and thymidine kinase. This same dose of CCK-LP caused after 8 h of treatment a marked and transient increase in pancreatic weight, activity of ODC, and concentration of putrescine. When secretin was added to 0.5 and 2.5 micrograms/kg/h of CCK-LP, no additional effect (except for ODC) was found. When secretin was added to the highest dose of CCK-LP, the decreased contents of protein and RNA were significantly increased, and the markedly increased activities of RNA- and DNA-synthesizing enzymes were significantly decreased. The present study shows a clear dose-response relationship for the trophic effect of CCK-LP on the rat pancreas and indicates that the growth effect of a supramaximal dose includes components of regeneration secondary to damage.(ABSTRACT TRUNCATED AT 250 WORDS)
Haarstad
H
H
Dept. of Medicine, Trondheim Regional Hospital, Norway.
Petersen
H
H
D000818:Animals; D015317:Biogenic Polyamines / Q000096:biosynthesis*; D002766:Cholecystokinin / Q000008:administration & dosage*; D004247:DNA / Q000032:analysis; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007262:Infusions, Intravenous; D008297:Male; D009929:Organ Size / Q000187:drug effects; D009955:Ornithine Decarboxylase / Q000378:metabolism; D010179:Pancreas / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D011506:Proteins / Q000032:analysis; D012313:RNA / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D012633:Secretin / Q000008:administration & dosage*
D015317:Biogenic Polyamines; D011506:Proteins; D012633:Secretin; D012313:RNA; D004247:DNA; D002766:Cholecystokinin; D012321:DNA-Directed RNA Polymerases; D009955:Ornithine Decarboxylase