PHARMACOLOGICAL STUDY OF GASTRIN-MEDIATED AMYLASE RELEASE IN PANCREATIC ACINAR-CELLS (AR4-2J)

In rat pancreatic acinar cells, amylase release and Ca2+ mobilization are related to the occupancy of CCKA receptor. The rat pancreatic acin ar cell line (AR4-2J) possesses both CCKA (CCKA R) and CCKB (CCKB R) s ub-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 antagonis t for CCKA R and PD 135158 a elective antagonist for CCKB R. We showed on AR4-2J cells that: a minority of CCKA R (K-d = 0.7 nM), a classica l CCKB R (K-d = 0.93 nM) and a new high affinity gastrin binding site (K, = 2.1 pM) coexisted; CCK through CCKA R and CCKB R, was more poten t to stimulate amylase secretion (EC(50) = 34 pM) and Ca2+ mobilizatio n (EC(50) = 30 pM) than to occupy its receptor. Gastrin induced a biph asic stimulation of amylase release. Gastrin through CCKB R was equall y potent to stimulate amylase release (EC(50) = 1.72 nM) and Ca2+ mobi lization (EC(50) = 3.1 nM), whereas through the high affinity gastrin binding site, gastrin-induced amylase release (EC(50) = 0.73 pM) did n ot correlate with the Ca2+ mobilization (EC(50) = 3.1 nM). These resul ts demonstrated for the first time the existence, on AR4-2J cells, of a high affinity gastrin receptor whose occupation by gastrin induces a mylase release.