The intrinsic nervous system of the gastrointestinal tract affects nearly aspect of digestive activity. While dysfunction of the autonomic nervous system has been postulated to cause or exacerbate several pancreatic diseases, little is known of the factors influencing signal processing and function of the enteropancreatic nervous system. As one of example, chronic pancreatitis is a devastating condition characterized by pain and exocrine insufficiency, in which abnormalities of neural function have been postulated to play a role. The current treatment of chronic pancreatitis is impiric, palliative and unsatisfactory, reflecting our lack of basic information. The following research project is designed to investigate on a fundamental level neural control mechanisms that have relevance to human health. We have hypothesized that: 1. Pancreatic nerves activate a functional domain consisting of multiple acini innervated by a single neuron; 2. Pancreatic neurotransmission is acutely regulated by presynaptic modulation of calcium-dependent signaling pathways; 3. For enteropancreatic neurons, long-term function is regulated, at the transcriptional level, by the duration and intensity of signaling activities; 4. In acinar cells, both enzyme secretion and gene expression are regulated via neural mechanisms.
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