ReviewAutonomic pathways regulating pancreatic exocrine secretion
Introduction
Autonomic innervation of the pancreas has been studied for over a century but its critical role in regulating exocrine secretion has only recently begun to be fully appreciated. Much of the early work established the effects of electrical stimulation or surgical and chemical disruption of large, mixed nerve trunks on secretion in vivo or in isolated, perfused organs. A plethora of potential neurotransmitters were also identified, although few were broadly and convincingly implicated exocrine secretion. Numerous recent reviews of the subject provide excellent detailed summaries of these earlier studies (Holst, 1993, Singer, 1993, Solomon, 1994, Owyang, 1996, Niebergall-Roth and Singer, 2001, Owyang and Williams, 2003). This review will focus rather on work, primarily from the last 20 years, defining the histology, neurochemistry, physiology, and pharmacology of pancreas-specific pathways; beginning in the CNS and ending at the neuroeffector synapses on acinar and duct epithelium and smooth muscle cells, and the microvasculature.
Section snippets
Vagal afferent neurons
Pancreatic vagal afferent neurons originate bilaterally in the nodose ganglia with the left and right ganglia predominantly innervating the duodenal and splenic lobes of the pancreas, respectively. Most of these small diameter (20 μ), capsaicin-sensitive sensory neurons contain substance P (SP) and/or calcitonin-gene related peptide (CGRP; Sharkey and Williams, 1983, Sharkey et al., 1984, Carobi, 1987, Rinaman and Miselis, 1987, Won et al., 1998). Anterograde tracing of nodose neurons labels
Pancreatic spinal afferent nerves
The pancreas receives spinal afferent innervation originating in T6-L2 (DRG), and traversing the splanchnic nerves and celiac plexus, before entering the pancreas mixed with postganglionic sympathetic nerves. Most of these capsaicin-sensitive, DRG neurons contain substance P (SP) and/or CGRP (Sharkey and Williams, 1983, Sharkey et al., 1984, Rinaman and Miselis, 1987, Won et al., 1998). Spinal afferents transmit both mechanoreceptive and nociceptive information to the preganglionic sympathetic
Innervation and neural regulation of acinar cells
Vagotomy or sympathectomy has little effect on acinar cell innervation, indicating it is primarily supplied by pancreatic neurons (Richins, 1945, Radke and Stach, 1986a, Radke and Stach, 1986b). Varicose nerve bundles in the interacinar spaces, often traveling with capillaries, supply fibers that pass over the surface of acinar cells with multiple varicosities (1–8) contacting single cells (Richins, 1945). Nerve terminals supplying acinar cells at the boundary with islets of Langerhans also
Conclusions
Multiple autonomic reflexes, central and peripheral, parasympathetic and sympathetic, monitor the contractile and luminal state of the GI tract, and blood glucose levels during digestion. These reflexes converge on, and are integrated with the intrinsic activity of, key populations of pre-and post-ganglionic efferent neurons that determine the final parasympathetic and sympathetic outflow to the pancreas. These reflexes appear to be tonically active, interactive, and, predominantly
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