HIGH-AFFINITY AND LOW-AFFINITY CCKA RECEPTOR STATES MEDIATE SPECIFIC GROWTH-INHIBITORY EFFECTS ON CHO CELLS

To relate specific effects on growth and transformation to activation of specific affinity states of the CCKA receptor stably expressed in CHO cells we compared responses to the CCK analogues JMV-180 and CCK8. CCK8 led to an inhibition of both cell proliferation and transformation. Effects on proliferation were indicated by a reduction of DNA synthesis and cell numbers. Effects on transformation were indicated by a reduction of colony formation in soft-agar. JMV-180 did not inhibit cell proliferation although a small inhibitory effect on DNA synthesis was observed. JMV-180 inhibited the maximal effects of CCK8 on cell proliferation and DNA synthesis. In contrast, JMV-180 substantially inhibited cell colony formation in soft-agar and did not inhibit the effects of CCK8 on this parameter. Collectively these data with receptor affinity state specific analogues indicated that inhibition of cell proliferation and growth in soft-agar can be attributed to activation of distinct affinity states. Thus, different second messengers are likely responsible for the inhibitory effects on anchorage-dependent and -independent growth. (C) 1995 Academic Press, Inc.