STIMULATION OF BOTH CCK-A AND CCK-B RECEPTORS ACTIVATES MAP KINASES IN AR42J AND RECEPTOR-TRANSFECTED CHO CELLS

It was recently found that cholecystokinin (CCK) activates mitogen-act ivated protein kinases (MAPK) in isolated rat pancreatic acini. The pr esent study evaluates whether one or both types of CCK receptors are c apable of MAPK activation in pancreatic AR42J acinar cells as well as CHO cells transfected with CCK-A or CCK-B receptors. CCK significantly increased p44 MAPK and p42 MAPK activities in AR42J cells. Minimal, h alf-maximal, and maximal responses were observed at 30 and 500 pM and 10 nM, respectively, after CCK-8 stimulation and at 100 pM and 1.5 and 30 nM, respectively, after gastrin stimulation. Glycine-extended gast rin had no effect at 100 nM and a small but significant effect at 1 mu M. The CCK-B receptor antagonist L365,260 almost totally blocked MAPK activation in AR42J cells after stimulation with gastrin and glycine- extended gastrin and substantially reduced the activation of both kina ses by CCK-8, while the CCK-A receptor antagonist L364,718 was much le ss effective. The CCK-A-selective agonist A71376, however, was an effe ctive stimulant of MAPK activity. In an alternative approach, stably t ransfected CHO cells bearing either CCK-A or CCK-B receptors were stim ulated with CCK-8. Each receptor induced a time-dependent increase in activity of both MAPKs by five-to sixfold in CCK-A-and CCK-B-bearing c ells. In conclusion, both CCK-A and CCK-B receptors activate MAPK in A R42J cells and in transfected CHO cells.