1999 Abstract: 2157 NEURONAL REGULATION OF PANCREATIC EXOCRINE SECRETION AND EARLY RESPONSE GENE TRANSCRIPTION
Abstracts
|
Recent evidence suggests a crucial role for the intrinsic nervous system of the gastrointestinal tract in nearly every aspect of digestive physiology, including pancreatic exocrine secretion. The mechanisms by which neurons signal pancreatic acinar cells are not well understood. In addition, whether short term stimuli induce the initiation of gene transcription, modulating long term fuction, is unknown. We hypothesized that neural mechanisms regulate pancreatic enzyme secretion in parallel with early response gene transcription. Methods: Rat pancreatic lobules, containing neurons in addition to acini, were harvested, maintained in an oxygenated physiologic buffer, and exposed to agonist (KCl or veratridine) with or without atropine (10-5M). Veratridine causes neuronal depolarization by opening fast sodium channels on axons, but has no effect on acinar cells. After exposure, lobules were 1) homogenized and analyzed for amylase content, and 2) fixed and probed with polyclonal c-fos antibody. Results expressed as mean ±SEM; ANOVA *p<0.05. Results: 1) Neuronal depolarization by KC1 or veratridine stimulated amylase release from pancreatic lobules (Figure 1). Tetrodotoxin, which blocks axonal sodium channels and acts as a specific inhibitor of veratridine, inhibited depolarization-induced amylase secretion. Atropine, which inhibits cholinergic neurotransmission, blocked amylase secretion in response to both KC1 and veratridine. Exposure to veratridine stimulated c-fos immunoreactivity in 24±12% of cells from pancreatic lobules, while untreated controls displayed no staining. The veratridine effects were abolished by co-incubation with atropine. Conclusions: Depolarization of intrapancreatic neurons stimulates acinar cells via a cholinergic mechanism, initiating amylase release and early response gene transcription. Intrapancreatic neurons regulate both secretory and transcriptional responses in acinar cells. Copyright 1996 - 1999, SSAT, Inc. |