CCK regulates pancreatic enzyme secretion via short duodenal-pancreatic reflexes in pigs.
BACKGROUND
Different routes of administration of CCK-33 and blockage of CCK-A and muscarinic (m3) receptors are used in this study to evaluate the mechanisms by which cholecystokinin can stimulate the exocrine pancreas.


METHODS
The experiment was performed on eight anaesthetized pigs during control conditions and after administration of the CCK-A and m3 receptor antagonists, Tarazepide and 4-DAMP, respectively. Catheters were surgically implanted in the pancreatic duct for juice collection and in the gastric and right gastro-epipoic arteries and in the jugular vein, so that infusions of CCK-33 could be made exclusively to the duodenum/stomach, duodenum/pancreas or general circulation, respectively.


RESULTS
Infusion of a low dose of CCK-33 (13 pmol kg(-1)) to the general circulation did not affect pancreatic protein or trypsin output. When the same dose was given directly to the duodenum/stomach or the duodenum/pancreas, pancreatic output increased during both control conditions and after Tarazepide and/or 4-DAMP treatment, though the increase in trypsin output was lower after Tarazepide and/or 4-DAMP blockade. A high dose of CCK-33 (130 pmol kg(-1)) given peripherally stimulated the pancreatic secretion, but this response was totally abolished in Tarazepide and 4-Damp treated animals.


CONCLUSIONS
Pancreatic enzyme secretion due to CCK-33 stimulation depends on the presence of short duodenal-pancreatic peptidergic reflexes evoked mainly via low sensitive, probably CCK-B, receptors located in the duodenum/stomach. Pancreatic secretion evoked by peripheral CCK-33 in pharmacological doses was independent of m3 receptors blockade but depended on CCK-A receptors located elsewhere than in the duodenum/pancreas.
Evilevitch
L
L
Dept. of Cell and Organism Biology, Lund University, Lund, Sweden. Lena.Evilevitch@zoofys.lu.se
Weström
B R
BR
Pierzynowski
S G
SG
D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology; D002766:Cholecystokinin / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D004386:Duodenum / Q000187:drug effects / Q000502:physiology*; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010179:Pancreas / Q000187:drug effects / Q000502:physiology*; D010189:Pancreatic Juice / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology; D043886:Receptor, Cholecystokinin A; D043587:Receptor, Muscarinic M3; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors; D011976:Receptors, Muscarinic / Q000378:metabolism; D012018:Reflex / Q000187:drug effects / Q000502:physiology*; D013552:Swine; D014357:Trypsin / Q000378:metabolism
D018727:Muscarinic Antagonists; D010880:Piperidines; D043886:Receptor, Cholecystokinin A; D043587:Receptor, Muscarinic M3; D011949:Receptors, Cholecystokinin; D011976:Receptors, Muscarinic; D001569:Benzodiazepines; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; D002766:Cholecystokinin; D014357:Trypsin; C118031:tarazepide