CONVERSION OF AMYLASE-SECRETING RAT PANCREATIC AR42J CELLS TO NEURON-LIKE CELLS BY ACTIVIN-A

When AR42J cells, an amylase-secreting pancreatic exocrine cell line, were treated with activin A, cells extended neuritelike processes, and , concomitantly, amylase-containing vesicles disappeared, Immunofluore scence and immunoelectron microscopy revealed that these processes had neurite-specific cytoskeletal architectures: neurofilaments and micro tubule bundles with cross-bridges of microtubule-associated protein 2, In addition to such morphological changes, activin-treated cells exhi bited a marked increase in cytoplasmic free calcium concentration in r esponse to depolarizing concentration of potassium, Moreover, activin- treated AR42J cells expressed mRNA for alpha(1) subunit of the neuroen docrine/beta cell-type voltage-dependent calcium channel, In naive AR4 2J cells, a sulfonylurea compound, tolbutamide, did not affect free ca lcium concentration, while it induced a marked elevation of free calci um in activin-treated cells, Single channel recording of the membrane patch revealed the existence of ATP-sensitive potassium channel in act ivin-treated cells, These results indicate that activin A converts amy lase-secreting AR42J cells to neuronlike cells, Given that pancreatic endocrine cells possess neuronlike properties and express ATP-sensitiv e potassium channel as well as neuroendocrine/beta cell-type voltage-d ependent calcium channel, activin treatment of AR42J cells may provide an in vitro model system to study the conversion of pancreatic exocri ne cells to endocrine cells in islets.