title: Pharmacological study of gastrin-mediated amylase release in pancreatic acinar cells (AR4-2J).
abstract: In rat pancreatic acinar cells, amylase release and Ca2+ mobilization are related to the occupancy of CCKA receptor. The rat pancreatic acinar cell line (AR4-2J) possesses both CCKA (CCKA R) and CCKB (CCKB R) sub-type receptors. Using this cell line we attempted to determine the relative involvement of each sub-type in both amylase release and Ca2+ mobilization. For this purpose we used L 364718 a selective antagonist for CCKA R and PD 135158 a selective antagonist for CCKB R. We showed on AR4-2J cells that: a minority of CCKA R (Kd = 0.7 nM), a classical CCKB R (Kd = 0.93 nM) and a new high affinity gastrin binding site (Kd = 2.1 pM) coexisted; CCK through CCKA R and CCKB R, was more potent to stimulate amylase secretion (EC50 = 34 pM) and Ca2+ mobilization (EC50 = 30 pM) than to occupy its receptor. Gastrin induced a biphasic stimulation of amylase release. Gastrin through CCKB R was equally potent to stimulate amylase release (EC50 = 1.72 nM) and Ca2+ mobilization (EC50 = 3.1 nM), whereas through the high affinity gastrin binding site, gastrin-induced amylase release (EC50 = 0.73 pM) did not correlate with the Ca2+ mobilization (EC50 = 3.1 nM). These results demonstrated for the first time the existence, on AR4-2J cells, of a high affinity gastrin receptor whose occupation by gastrin induces amylase release.
authors.affiliation: INSERM U 151, Institut Fédératif de Recherches Louis Bugnard, CHU Rangueil, Toulouse, France.
authors.forename: V
authors.initials: V
authors.lastname: Bertrand
authors.forename: M J
authors.initials: MJ
authors.lastname: Bastié
authors.forename: C
authors.initials: C
authors.lastname: Bigaud
authors.forename: S
authors.initials: S
authors.lastname: Pyronnet
authors.forename: N
authors.initials: N
authors.lastname: Vaysse
authors.forename: L
authors.initials: L
authors.lastname: Pradayrol
mesh_terms: D000681:Amylases / Q000378:metabolism*; D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002766:Cholecystokinin / Q000378:metabolism; D020109:Devazepide; D005755:Gastrins / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008536:Meglumine / Q000031:analogs & derivatives / Q000494:pharmacology; D010179:Pancreas / Q000201:enzymology*; D010189:Pancreatic Juice / Q000378:metabolism*; D051381:Rats; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D001570:Benzodiazepinones; D005755:Gastrins; D007211:Indoles; D011949:Receptors, Cholecystokinin; C065600:PD 135158; D008536:Meglumine; D002766:Cholecystokinin; D000681:Amylases; D020109:Devazepide; D002118:Calcium