Conversion of amylase-secreting rat pancreatic AR42J cells to neuronlike 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. 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.
Ohnishi
H
H
Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan.
Ohgushi
N
N
Tanaka
S
S
Mogami
H
H
Nobusawa
R
R
Mashima
H
H
Furukawa
M
M
Mine
T
T
Shimada
O
O
Ishikawa
H
H
D028341:Activins; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000681:Amylases / Q000096:biosynthesis*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D003599:Cytoskeleton / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D005455:Fluorescent Antibody Technique; D006133:Growth Substances / Q000494:pharmacology; D007265:Inhibins / Q000494:pharmacology*; D007700:Kinetics; D016253:Microscopy, Immunoelectron; D008869:Microtubule-Associated Proteins / Q000032:analysis / Q000096:biosynthesis; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology*; D010179:Pancreas / Q000166:cytology* / Q000201:enzymology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D051381:Rats; D014044:Tolbutamide / Q000494:pharmacology; D014404:Tubulin / Q000032:analysis
D006133:Growth Substances; D008869:Microtubule-Associated Proteins; D015221:Potassium Channels; D014404:Tubulin; D028341:Activins; D007265:Inhibins; D000255:Adenosine Triphosphate; D014044:Tolbutamide; D000681:Amylases