The amphicrine pancreatic cell line AR42J: a model system for combined studies on exocrine and endocrine secretion

Secretory vesicles of both the exocrine and the endocrine pancreas have been isolated and characterized in molecular terms from pancreatic tissue and primary cell cultures. Studies on pancreatic secretory processes could be further facilitated by the use of permanent cell lines that respond to secretory stimuli with a regulated secretory response. We now present biochemical, morphological and secretory studies on the rat pancreatic acinar cell line AR42J. This cell line is characterized by the presence of digestive enzyme-containing dense core vesicles, which are released in response to cholecystokinin. In addition, we present evidence that these cells also contain small neuroendocrine-specific vesicles, as evidenced by the expression of the neuroendocrine-specific vesicle proteins synaptophysin and S.V.2. Corresponding to these mixed exocrine-neuroendocrine features, we also found considerable amounts of the neurotransmitters glycine, glutamine and gamma-aminobutyric acid (GABA), as well as the rate-limiting enzyme in GABA synthesis, glutamic acid decarboxylase (GAD) (EC 4.1.1.15) expressed in these cells. We demonstrated a specific uptake mechanism for radioactively-labelled GABA by these cells. In addition, GABA was released from intracellular storage pools by nicotinic receptor stimulation or membrane depolarization. In summary, AR42J cells represent the first amphicrine pancreatic cell line with the combined expression of exocrine and neuroendocrine secretory organelles, both of which follow a regulated secretory pathway in response to various secretory stimuli.