CORRELATION BETWEEN THE STIMULATION OF C-FOS GENE-EXPRESSION AND DNA-SYNTHESIS IN RAT PANCREATIC ACINAR-CELLS IN-VITRO

The molecular mechanisms involved in the regulation of pancreatic acin ar cell growth are unknown. In order to understand the role of c-fos e xpression in the effects of stimulants on pancreatic acinar cell grown we compared the effects of stimulants on DNA synthesis and c-fos gene expression in vitro. In particular we examined the effects of activat ing high and low affinity states of the CCK receptor on these two grow th parameters. JMV-180 is a CCK analog that interacts in the rat with the high affinity state as an agonist and the low affinity state as an antagonist. CCK8 and JMV-180 each stimulated increases in DNA synthes is and c-fos gene expression. However, within the same experiment the effects of CCK were significantly greater than those of JMV-180. Furth ermore, JMV-180 inhibited the maximal effects of CCK8 on both growth p arameters. These data indicate that the high affinity CCK receptor sta te is capable of stimulating both DNA synthesis and c- fos gene expres sion. However, the low affinity state is also important for the full r esponse to CCK8. With either CCK analog the effects on DNA synthesis a nd c-fos gene expression were well correlated. To determine the genera lity of these findings the effects of secretin and carbachol on growth parameters was examined. Secretin did not stimulate either parameter. In contrast, carbachol caused a large stimulation of c-fos expression and had no effect on DNA synthesis in vitro. Thus, c-fos expression m ay be necessary but is not sufficient for stimulation of pancreatic ac inar cell growth.