The action of caerulein on pancreatic secretion of the dog and biliary secretion of the dog and the rat.
1. Caerulein displayed a potent stimulant action on pancreatic secretion in the dog. Threshold doses were 1-5 ng/kg by rapid intravenous injection, 0.25-1 ng/kg per min by intravenous infusion and 50-100 ng/kg by subcutaneous injection. There was a conspicuous increase not only in the volume flow of pancreatic juice but also in the output of solid constituents of the juice and of amylase. However, continuous stimulation of pancreatic secretion by intravenous infusion of caerulein resulted in a progressive reduction of the amylase concentration and still more of the dry residue content of pancreatic juice. The bicarbonate concentration in pancreatic juice produced by caerulein was similar to that observed in juice secreted following pancreozymin administration or following other stimuli causing the same rate of flow of pancreatic juice.2. On a molar basis, caerulein was 25-30 times as active as human gastrin I and 3-6 times as active as cholecystokinin-pancreozymin. The presence in the molecule of caerulein of a sulphated tyrosyl residue at position 4 of the decapeptide (position 7 starting from the C-terminus) was a necessary prerequisite for the manifestation of the cholecystokinin-pancreozymin-like actions of caerulein. The C-terminal heptapeptide of caerulein retained much of the activity of the intact caerulein molecule.3. At high dose levels (50-200 ng/kg in the dog, 1 mug/kg in the rat, by rapid intravenous injection) caerulein stimulated the flow of hepatic bile in the dog and the rat. The dry residue of the bile and the cholesterol concentration were appreciably greater in rats treated with caerulein than in control rats.4. The activity spectrum of caerulein was identical with that of cholecystokinin-pancreozymin. This is readily explained on the basis of the almost identical structure of the C-terminal octapeptide of the two peptides.5. Caerulein and some caerulein-like peptides may be considered as model peptides, capable of being substituted for cholecystokinin-pancreozymin in all the possible experimental and clinical uses of the duodenal hormone, with the important advantage that they are more easily available.6. The question is raised whether cholecystokinin-pancreozymin obtained from the duodenum by acid extraction is the authentic hormone or rather a carrier polypeptide from which a smaller active peptide may be set free, when needed, into the circulation.
D000681:Amylases / Q000032:analysis; D000818:Animals; D001639:Bicarbonates / Q000032:analysis; D001646:Bile / Q000032:analysis / Q000378:metabolism*; D002766:Cholecystokinin / Q000494:pharmacology; D004285:Dogs; D005260:Female; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008099:Liver / Q000187:drug effects; D008297:Male; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D010189:Pancreatic Juice / Q000032:analysis; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats
D001639:Bicarbonates; D010455:Peptides; D002766:Cholecystokinin; D000681:Amylases
Am J Physiol. 1965 Nov;209(5):966-72
5849500
Am J Physiol. 1966 Mar;210(3):629-34
5933217
Am J Physiol. 1966 May;210(5):1153-9
5947262
Acta Physiol Scand. 1967 Jan-Feb;69(1):23-8
6031389
Gastroenterology. 1968 May;54(5):907-12
5652525
Lancet. 1968 Jun 29;1(7557):1435
4173024
Br J Pharmacol Chemother. 1968 May;33(1):59-71
5660166
Experientia. 1968 Aug 15;24(8):771-3
5693208
Br J Pharmacol. 1968 Oct;34(2):291-310
5687588
Br J Pharmacol. 1968 Oct;34(2):311-29
4879882
Lancet. 1969 Mar 15;1(7594):580-1
4179878
Scand J Gastroenterol. 1968;3(6):637-40
5731261
J Biol Chem. 1950 Nov;187(1):97-106
14794694