Cholecystokinin and gastrin peptides stimulate ODC activity in a rat pancreatic cell line.
Recent studies have demonstrated that cholecystokinin (CCK) receptors are heterologous in peripheral tissues and in the central nervous system and that CCK-gastrin (CCK-G) peptides are potent trophic factors for the gastrointestinal tract. In the present study we used 125I-labeled gastrin and 125I-labeled CCK to demonstrate the heterogeneity of CCK receptors on a rat pancreatic acinar cell line (AR4-2J) and analyze the role of these receptors in increasing the activity of ornithine decarboxylase. Pharmacological analysis of radioligand binding fit well with the presence of two different receptors: 1) a CCK-selective receptor having the characteristics of the CCK receptor present on normal pancreatic cells and 2) a high-affinity, low-selectivity CCK-G binding site that interacts with all CCK-G peptides sulfated and nonsulfated. CCK-G peptides stimulate ornithine decarboxylase activity with the following order of potencies (EC50): G-(2-17)-ds (0.1 nM) greater than or equal to CCK-9 (0.25 nM) greater than or equal to pentagastrin (0.4 nM) greater than CCK-4 (6 nM). This stimulation was not inhibited by CCK antagonist (asperlicin) at a concentration range that blocks the CCK receptor but does not compete with 125I-labeled gastrin binding to the CCK-G receptor. These results, obtained with CCK-G agonists and antagonists, demonstrate that ornithine decarboxylase stimulation in these cells is mediated via the CCK-G receptor.
Scemama
J L
JL
Institut National de la Santé et de la Recherche Médicale U151, Toulouse, France.
De Vries
L
L
Pradayrol
L
L
Seva
C
C
Tronchere
H
H
Vaysse
N
N
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002460:Cell Line; D002766:Cholecystokinin / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005755:Gastrins / Q000494:pharmacology*; D009955:Ornithine Decarboxylase / Q000032:analysis*; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D011949:Receptors, Cholecystokinin / Q000032:analysis / Q000187:drug effects
D001570:Benzodiazepinones; D005755:Gastrins; D011949:Receptors, Cholecystokinin; D002766:Cholecystokinin; D009955:Ornithine Decarboxylase; C046367:asperlicin