ACTIVIN-A - NEGATIVE REGULATOR OF AMYLASE SECRETION AND CELL-PROLIFERATION IN RAT PANCREATIC ACINAR AR42J CELLS

Activin A, a member of the transforming growth factor-p supergene fami ly, exists in secretory granules of non-B-cells of rat pancreatic isle t (H. Yasuda, K. Inoue, H. Shibata, T. Takeuchi, Y. Eto, Y. Hasegawa, N. Sekine, Y. Totsuka, T. Mine, E. Ogata, and I. Kojima. Endocrinology 133: 624-630, 1993). Because functions of exocrine pancreas are influ enced by hormones in pancreatic islet, it is possible that activin A a ffects the function of pancreatic acinar cells. To examine this possib ility, we studied the effects of activin A on amylase secretion and DN A synthesis in AR42J cells. In these cells, dexamethasone !Dr) induces increases in secretory organelles and secretion of amylase (C. D. Log sdon, J. Moessner, J. A. Williams, and I. D. Goldfine. J. Cell Biol. 1 00: 1200-1208 1985). Activin A did not change the rate of amylase rele ase by itself nor affect the cholecystokinin-stimulated amylase releas e from Dr-treated differentiated AR42J cells. However, when activin A was added together with Dx, activin A inhibited Dx-induced increase in amylase content in a dose-dependent manner. In the presence of 1 nM a ctivin A, the effect of Dx was abolished. In the absence of Dx, amylas e content of the cells was also reduced by activin A in a dose-depende nt manner. The maximum inhibitory effect was obtained by 10 nM activin A, and at this concentration amylase content became undetectable. In addition, activin A potently inhibited DNA synthesis as assessed by [H -3]thymidine incorporation. The maximal inhibitory effect was obtained by 10 nM activin A, and [H-3]thymidine incorporation was similar to 3 9 of the control value. Electron microscopic analysis revealed that in activin A-treated cells, crinophagy-like structures were observed. Ro ugh endoplasmic reticulum disappeared, and only free ribosomes were ob served. These results indicate that activin A inhibits both proliferat ion and amylase production in AR42J cells.