CHOLECYSTOKININ-B GASTRIN RECEPTORS MEDIATE RAPID FORMATION OF ACTIN STRESS FIBERS/

Specific receptors for brain-gut peptide hormones, cholecystokinin (CC K) and gastrin, are expressed in a variety of human tumor cells, CCK a nd gastrin promote the growth of NIH3T3 cells into which the CCK-B/gas trin receptor had been introduced via a eukaryotic expression vector. In this study, we have examined the effect of CCK-8 on the actin cytos keleton by using two mouse fibroblast cell lines expressing human CCK- B/gastrin receptors. Treatment with very low concentrations of CCK-8 ( 10(-10) M) induced the formation of actin stress fibers within one min ute. Stress fiber formation increased for 30 min, In contrast, a poten t mitogen for fibroblasts, platelet-derived growth factor (PDGF), init ially induced membrane ruffling and, later, a weak formation of stress fibers. Microinjection of rho GDP dissociation inhibitor or Clostridi um botulinum ADP-ribosyltransferase C3 which is known to impair the fu nction of a small GTP-binding protein, rho p21, inhibited the stress f iber formation by CCK-8 as well as by PDGF. These results indicate tha t CCK-B/gastrin receptor could regulate stress fiber formation in a rh o p21-dependent manner. The signals from CCK-B/gastrin receptor might affect cell growth as well as cell motility or adhesion by regulating the actin cytoskeleton.