Physicians

Department / Division
Medicine / Medicine - Gastroenterology

Address
DUMC 3913
Durham, NC 27710

Appointment Telephone
Not accepting new patients

Office Telephone
919-681-6380

Fax Telephone
919-668-0412

Training

• MD, Vanderbilt University School of Medicine (Tennessee), 1978

Residency

• Internal Medicine, University of California–San Francisco Medical Center, 1978-1981
• Gastroenterology, University of California–San Francisco Medical Center, 1981-1984

Clinical Interests
Hormone-producing tumors of the GI tract, pancreatitis, research, teaching

Research Interests
Our laboratory is interested in the physiology of the gastrointestinal hormone cholecystokinin (CCK). CCK is secreted from the upper small intestine in response to eating and has a variety of actions on various target tissues including the gallbladder, stomach, intestines, endocrine and exocrine pancreas, and the central nervous system. Studies have utilized a recently developed and specific bioassay method for measuring plasma levels of CCK. With this assay, we have investigated the physiologic role of CCK to stimulate gallbladder contraction, endocrine secretion, and satiety. Currently, we are studying the hormonal mechanisms that regulate CCK secretion and intestinal CCK gene expression. Further studies are directed at determining the intracellular signalling pathways regulating CCK secretion in vitro.

A second major interest of our laboratory is pancreatitis. We are actively engaged in determining the pathogenic mechanisms of pancreatitis using experimental models. Currently we are concentrating on two pathways: (1) neurogenic inflammation in pancreatitis and (2) the role of endogenous trypsin inhibitors in the development of pancreatitis. Neurogenic inflammation results from the activation of specific sensory neurons causing the release of bioactive substances from nerve terminals resulting in vasodilatation, edema, and other manifestations of inflammation. Our goal is to identify the agents that activate sensory neurons, the receptors on sensory nerves that mediate these actions and the effects of neural stimulation on pancreatic injury. Our long-term goal is to develop strategies directed at reducing neurogenic inflammation as an approach to prevent pancreatitis.

Endogenous trypsin inhibitors within the pancreas are believed to limit the protease activity within the pancreas. We proposed that they could also prevent possible deleterious effects of pancreatic enzymes that become activated within the pancreas during pancreatitis. Our laboratory has recently created a transgenic mouse that overexpresses pancreatic secretory trypsin inhibitor. Preliminary data indicate that this mouse is resistant to experimental pancreatitis. We are actively engaged in studies to characterize the role of this protein in the pathogenesis of pancreatitis.

Industry Relationships and Collaborations (What's this?)

This faculty member has no reported relationships with industry.

Representative Publications
Nathan, JD; Peng, RY; Wang, Y; McVey, DC; Vigna, SR; Liddle, RA. Primary sensory neurons: a common final pathway for inflammation in experimental pancreatitis in rats. American Journal of Physiology: Gastrointestinal and Liver Physiology. 2002;283:G938-G946. (2002) Abstract

Wang, Y; Prpic, V; Green, GM; Reeve, JR; Liddle, RA. Luminal CCK-releasing factor stimulates CCK release from human intestinal endocrine and STC-1 cells. American Journal of Physiology: Gastrointestinal and Liver Physiology. 2002;282:G16-G22. (2002) Abstract

Nathan, JD; Patel, AA; McVey, DC; Thomas, JE; Prpic, V; Vigna, SR; Liddle, RA. Capsaicin vanilloid receptor-1 mediates substance P release in experimental pancreatitis. American Journal of Physiology: Gastrointestinal and Liver Physiology. 2001;281:G1322-G1328. (2001) Abstract

Prpic, V; Fitz, JG; Wang, Y; Raymond, JR; Garnovskaya, MN; Liddle, RA. Inhibition of Na+/H+ exchange stimulates CCK secretion in STC-1 cells. American Journal of Physiology. 1998;275:G689-G695. (1998) Abstract

Liddle, RA. Cholecystokinin cells. Annual Review of Physiology. 1997;59:221-242. (1997) Abstract

Spannagel, AW; Green, GM; Guan, D; Liddle, RA; Faull, K; Reeve, JR. Purification and characterization of a luminal cholecystokinin-releasing factor from rat intestinal secretion. Proceedings of the National Academy of Sciences of USA. 1996;93:4415-4420. (1996) Abstract

Liddle, RA. Regulation of cholecystokinin secretion by intraluminal releasing factors. American Journal of Physiology. 1995;269:G319-G327. (1995) Abstract