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 C HO cells we compared responses to the CCK analogues JMV-180 and CCK8. CCK8 led to an inhibition of both cell proliferation and transformatio n. Effects on proliferation were indicated by a reduction of DNA synth esis and cell numbers. Effects on transformation were indicated by a r eduction of colony formation in soft-agar. JMV-180 did not inhibit cel l proliferation although a small inhibitory effect on DNA synthesis wa s observed. JMV-180 inhibited the maximal effects of CCK8 on cell prol iferation and DNA synthesis. In contrast, JMV-180 substantially inhibi ted cell colony formation in soft-agar and did not inhibit the effects of CCK8 on this parameter. Collectively these data with receptor affi nity state specific analogues indicated that inhibition of cell prolif eration and growth in soft-agar can be attributed to activation of dis tinct affinity states. Thus, different second messengers are likely re sponsible for the inhibitory effects on anchorage-dependent and -indep endent growth. (C) 1995 Academic Press, Inc.