title: New insights into neurohormonal regulation of pancreatic secretion.
abstract: The existence of high- and low-affinity cholecystokinin (CCK)-A receptors on rodent pancreatic acini is well established. Until recently, CCK was believed to act directly on pancreatic acini to stimulate pancreatic secretion in both rodents and humans. However, conclusive evidence that human pancreatic acini lack functional CCK-A receptors has been presented. Despite substantial differences in rodent and human pancreatic physiology, CCK appears to act via vagal cholinergic pathways to mediate pancreatic secretion in both species. Structural and functional evidence suggests that CCK acts on vagal afferent fibers, which may explain how CCK doses that produce physiologic plasma CCK levels act via vagal cholinergic pathways to stimulate pancreatic secretion. Although most knowledge of vagal CCK-A receptors comes from research on rodents, physiologic studies suggest that this information is applicable to humans. In contrast to its effect on satiety, which is mediated by low-affinity vagal CCK-A receptors, CCK acts through high-affinity CCK-A receptors to evoke pancreatic secretion, suggesting that different affinity states of the vagal CCK receptors mediate different digestive functions. Vagal afferent pathways also transmit sensory information about the mechanical and physiochemical state of the digestive tract, mediated in part by serotonin, which, in turn, influences pancreatic secretion. A synergistic interaction between CCK and serotonin at the level of the nodose ganglia may explain the robust postprandial pancreatic secretion despite a modest postprandial increase in plasma CCK. Important physiologically, these findings not only explain discrepancies in previous in vivo vs. in vitro studies, but they revolutionize our current concept of the mechanism of CCK on pancreatic exocrine secretion.
authors.affiliation: Department of Internal Medicine, 3912 Taubman Center, University of Michigan Health System, Ann Arbor, Michigan 48109-0362, USA. cowyang@umich.edu
authors.forename: Chung
authors.initials: C
authors.lastname: Owyang
authors.forename: Craig D
authors.initials: CD
authors.lastname: Logsdon
mesh_terms: D000818:Animals; D002766:Cholecystokinin / Q000502:physiology; D002799:Cholinergic Fibers / Q000502:physiology; D006801:Humans; D009434:Neural Pathways / Q000502:physiology; D018377:Neurotransmitter Agents / Q000502:physiology; D009620:Nodose Ganglion / Q000502:physiology; D010179:Pancreas / Q000294:innervation* / Q000378:metabolism* / Q000502:physiology; D019518:Postprandial Period; D043886:Receptor, Cholecystokinin A / Q000502:physiology; D011949:Receptors, Cholecystokinin / Q000502:physiology*; D012701:Serotonin / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014630:Vagus Nerve / Q000502:physiology*; D017833:Visceral Afferents / Q000502:physiology*
chemical_list: D018377:Neurotransmitter Agents; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin; D012701:Serotonin; D002766:Cholecystokinin