Activin A: negative regulator of amylase secretion and cell proliferation in rat pancreatic acinar AR42J cells
Yasuda, H.; Tanaka, S.; Ohnishi, H.; Mashima, H.; Ogushi, N.; Mine, T.; Kojima, I.
American Journal of Physiology 267(2 Pt 1): G220-G226
1994
ISSN/ISBN: 0002-9513 PMID: 7521134 Document Number: 434300
Activin A, a member of the transforming growth factor-beta supergene family, exists in secretory granules of non-B-cells of rat pancreatic islet (H. Yasuda, K. Inoue, H. Shibata, T. Takeuchi, Y. Eto, Y. Hasegawa, N. Sekine, Y. Totsuka, T. Mine, E. Ogata, and 1. Kojima. Endocrinology 133: 624-630, 1993). Because functions of exocrine pancreas are influenced by hormones in pancreatic islet, it is possible that activin A affects the function of pancreatic acinar cells. To examine this possibility, we studied the effects of activin A on amylase secretion and DNA synthesis in AR42J cells. In these cells, dexamethasone (Dx) induces increases in secretory organelles and secretion of amylase (C. D. Logsdon, J. Moessner, J. A. Williams, and I. D. Goldfine. J. Cell Biol. 100: 1200-1208 1985). Activin A did not change the rate of amylase release by itself nor affect the cholecystokinin-stimulated amylase release from Dx-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 activin A, the effect of Dx was abolished. In the absence of Dx, amylase content of the cells was also reduced by activin A in a dose-dependent 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 (3H)thymidine incorporation. The maximal inhibitory effect was obtained by 10 nM activin A, and (3H)thymidine incorporation was apprx 3% of the control value. Electron microscopic analysis revealed that in activin Atreated cells, crinophagy-like structures were observed. Rough endoplasmic reticulum disappeared, and only free ribosomes were observed. These results indicate that activin A inhibits both proliferation and amylase production in AR42J cells.