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Research Article Free access | 10.1172/JCI107790

Vasoactive Intestinal Peptide Stimulation of Adenylate Cyclase and Active Electrolyte Secretion in Intestinal Mucosa

Charles J. Schwartz, Daniel V. Kimberg, Harland E. Sheerin, Michael Field, and Sami I. Said

Department of Medicine, Harvard Medical School, Boston 02215

Gastrointestinal Unit of the Department of Medicine, Beth Israel Hospital, Boston 02215

Department of Internal Medicine, University of Texas Southwestern Medical School, Dallas, Texas 75216

Veterans Administration Hospital, Dallas, Texas 75235

Find articles by Schwartz, C. in: JCI | PubMed | Google Scholar

Department of Medicine, Harvard Medical School, Boston 02215

Gastrointestinal Unit of the Department of Medicine, Beth Israel Hospital, Boston 02215

Department of Internal Medicine, University of Texas Southwestern Medical School, Dallas, Texas 75216

Veterans Administration Hospital, Dallas, Texas 75235

Find articles by Kimberg, D. in: JCI | PubMed | Google Scholar

Department of Medicine, Harvard Medical School, Boston 02215

Gastrointestinal Unit of the Department of Medicine, Beth Israel Hospital, Boston 02215

Department of Internal Medicine, University of Texas Southwestern Medical School, Dallas, Texas 75216

Veterans Administration Hospital, Dallas, Texas 75235

Find articles by Sheerin, H. in: JCI | PubMed | Google Scholar

Department of Medicine, Harvard Medical School, Boston 02215

Gastrointestinal Unit of the Department of Medicine, Beth Israel Hospital, Boston 02215

Department of Internal Medicine, University of Texas Southwestern Medical School, Dallas, Texas 75216

Veterans Administration Hospital, Dallas, Texas 75235

Find articles by Field, M. in: JCI | PubMed | Google Scholar

Department of Medicine, Harvard Medical School, Boston 02215

Gastrointestinal Unit of the Department of Medicine, Beth Israel Hospital, Boston 02215

Department of Internal Medicine, University of Texas Southwestern Medical School, Dallas, Texas 75216

Veterans Administration Hospital, Dallas, Texas 75235

Find articles by Said, S. in: JCI | PubMed | Google Scholar

Published September 1, 1974 - More info

Published in Volume 54, Issue 3 on September 1, 1974
J Clin Invest. 1974;54(3):536–544. https://doi.org/10.1172/JCI107790.
© 1974 The American Society for Clinical Investigation
Published September 1, 1974 - Version history
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Abstract

Vasoactive intestinal peptide (VIP), originally isolated from hog small intestinal mucosa, has been shown to cause small intestinal secretion. More recently, this peptide has been identified in the plasma and tumors of patients with the so-called “pancreatic cholera” syndrome. In order to explore the possible role of VIP in the pathogenesis of this syndrome, we examined the effects of this peptide and other hormones on the cyclic AMP levels, adenylate cyclase activity, and ion transport in in vitro preparations of ileal mucosa. In rabbit ileal mucosa, VIP (20 μg/ml) caused a prompt fivefold increase in cyclic AMP level, whereas nine other hormones, which have been postulated to cause intestinal secretion, failed to exert such an effect. Pentagastrin and glucagon also failed to increase cyclic AMP levels in canine ileal mucosa. An increase in mucosal cyclic AMP levels was observed at a VIP concentration of 0.1 μg/ml and appeared to be nearly maximal at 2.0 μg/ml. VIP (100 μg/ml) stimulated adenylate cyclase activity in a membrane preparation from rabbit ileal mucosa. Secretin (6.0 × 10-5 M) failed to do so. When added to the serosal side of isolated rabbit ileal mucosa clamped in an Ussing chamber, VIP (2 μg/ml) increased short-circuit current (SCC) and caused net secretion of both Cl and Na. Net Cl secretion exceeded net Na secretion. These effects of VIP on mucosal cyclic AMP metabolism and ion transport are similar to those observed with cholera enterotoxin and certain prostaglandins. VIP was also tested with normal human ileal mucosa. At a concentration of 2 μg/ml it caused a fivefold increase in cyclic AMP level and an increase in SCC of the same magnitude as that caused by 5 mM theophylline. Addition of a second 2-μg/ml dose of VIP and addition of theophylline after VIP produced no further change in SCC. We conclude the VIP stimulates adenylate cyclase and active ion secretion in both rabbit and human ileal mucosa. This may be related to the pathogenesis of diarrhea in patients with the pancreatic cholera syndrome.

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