CCK-B RECEPTORS PRODUCE SIMILAR SIGNALS BUT HAVE OPPOSITE GROWTH EFFECTS IN CHO AND SWISS 3T3 CELLS

Rat cholecystokinin-B (CCK-B) receptors were transfected into Chinese hamster ovary (CHO)-K1 (CHO-CCK-B) and Swiss 3T3 (Swiss 3T3-CCK-B) cel ls, and the effects of receptor activation on cell proliferation and i ntracellular signaling were investigated. CCK octapeptide (CCK-8) trea tment had no effect on cell growth in quiescent CHO-CCK-B cells but in hibited DNA synthesis, proliferation, and colony formation when the ce lls were grown in fetal bovine serum (FBS). In contrast, CCK-8 stimula ted DNA synthesis in quiescent Swiss 3T3-CCK-B cells and had no effect when the cells were grown in FBS. These differences in growth respons es were not due to differences in the level of receptor expression, as similar numbers of receptors were present in both cell types. To dete rmine whether the different growth effects were due to differences in receptor coupling to common second messenger pathways, we investigated the effects of CCK-8 on several known intracellular signals. In both cell types, CCK-8 stimulated increases in intracellular Ca2+ concentra tion and polyphosphoinositide hydrolysis with similar potencies and ef ficacies. CCK-8 also stimulated arachidonate release from both cell ty pes, although the potency was higher in the CHO cells. Adenosine 3',5' -cyclic monophosphate generation was observed at high agonist concentr ations in both cell types and was much greater in cells with higher re ceptor density. In summary, receptor activation had opposite effects o n growth parameters in CHO and Swiss 3T3 cells, but only minor differe nces were observed in the characteristics of CCK-B receptor coupling t o specific second messengers in the two cell types. Thus cellular cont ext is a principal determinant of the biological effects of CCK-B rece ptor activation, and differences in biological responses may occur ind ependently of major differences in receptor coupling.