Conversion of amylase-secreting rat pancreatic AR42J cells to neuronlike cells by activin A.

H Ohnishi; N Ohgushi; S Tanaka; H Mogami; R Nobusawa; H Mashima; M Furukawa; T Mine; O Shimada; H Ishikawa

doi:10.1172/JCI117922

Conversion of amylase-secreting rat pancreatic AR42J cells to neuronlike cells by activin A.

H Ohnishi, N Ohgushi, S Tanaka, H Mogami, R Nobusawa, H Mashima, M Furukawa, T Mine, O Shimada, and H Ishikawa

Published May 1, 1995 - More info

View PDF

Abstract

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. Immunofluorescence and immunoelectron microscopy revealed that these processes had neurite-specific cytoskeletal architectures: neurofilaments and microtubule bundles with cross-bridges of microtubule-associated protein 2. In addition to such morphological changes, activin-treated cells exhibited a marked increase in cytoplasmic free calcium concentration in response to depolarizing concentration of potassium. Moreover, activin-treated AR42J cells expressed mRNA for alpha 1 subunit of the neuroendocrine/beta cell-type voltage-dependent calcium channel. In naive AR42J cells, a sulfonylurea compound, tolbutamide, did not affect free calcium concentration, while it induced a marked elevation of free calcium in activin-treated cells. Single channel recording of the membrane patch revealed the existence of ATP-sensitive potassium channel in activin-treated cells. These results indicate that activin A converts amylase-secreting AR42J cells to neuronlike cells. Given that pancreatic endocrine cells possess neuronlike properties and express ATP-sensitive potassium channel as well as neuroendocrine/beta cell-type voltage-dependent calcium channel, activin treatment of AR42J cells may provide an in vitro model system to study the conversion of pancreatic exocrine cells to endocrine cells in islets.

Images.