Caerulein and gastrin(2-17 ds) regulate differently synthesis of secretory enzymes, mRNA levels and cell proliferation in pancreatic acinar cells (AR4-2J).
In order to characterize the biological functions coupled to cholecystokinin (CCK) A and B receptors, the effects of gastrin(2-17 ds) and caerulein were compared. An isolated cell model, the pancreatic acinar cell line AR4-2J, was used and the experiments were carried out in serum-free media. Caerulein was found to evoke no mitogenic effects either alone or in the presence of the CCK antagonists L364,718 and CR1409. Gastrin(2-17 ds) increased cell proliferation by 2-fold with an IC50 of 150 pM, corresponding to the occupancy of the CCK B receptors. CR1409, at concentrations that fully occupied CCK B receptors, inhibited the gastrin(2-17 ds) effects. Caerulein enhanced chymotrypsinogen biosynthesis by 100% and the corresponding mRNA level by 75%; amylase biosynthesis and mRNA level were enhanced by 40% only. Half-maximal increases in chymotrypsin activity and mRNA level were recorded in response to caerulein at concentrations of 100 pM and 50 pM respectively. Gastrin(2-17 ds) at 100 nM enhanced chymotrypsinogen biosynthesis by 26% and its mRNA level by 35%; these responses were lower than those evoked by 0.1 nM caerulein. Furthermore, CR1409 completely inhibited caerulein- and gastrin(2-17 ds)-stimulated chymotrypsinogen synthesis, with similar IC50 (4 microM). These results suggest that both peptides induced the synthesis of the secretory enzyme after occupancy of CCK A receptors.
Pradel
P
P
Groupe de Recherche de Biologie et Pathologie Digestive (INSERM U151), CHU Rangueil, Toulouse, France.
Estival
A
A
Seva
C
C
Wicker-Planquart
C
C
Puigserver
A
A
Vaysse
N
N
Clemente
F
F
D000681:Amylases / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002108:Ceruletide / Q000494:pharmacology*; D002766:Cholecystokinin / Q000378:metabolism; D002919:Chymotrypsinogen / Q000096:biosynthesis* / Q000235:genetics; D004790:Enzyme Induction / Q000187:drug effects; D005755:Gastrins / Q000494:pharmacology*; D010179:Pancreas / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D010446:Peptide Fragments / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011949:Receptors, Cholecystokinin / Q000378:metabolism
D005755:Gastrins; D010446:Peptide Fragments; D012333:RNA, Messenger; D011949:Receptors, Cholecystokinin; C072989:gastrin (2-17), desulfonated-; D002108:Ceruletide; D002766:Cholecystokinin; D002919:Chymotrypsinogen; D000681:Amylases