Vasoactive intestinal polypeptide: elevated plasma and tissue levels in the watery-diarrhea syndrome due to pancreatic and other tumors.
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Biomedical subjects
Publications and source records attributed to S I Said.
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Hypoxic ventilation of isolated perfused cat lungs caused the frequent appearance in pulmonary perfusates of biologically active substances, which included prostaglandins or prostaglandin-like compounds. In anesthetized cats, inhibition of prostaglandin biosynthesis with infusions of aspirin (more than 50 milligrams per kilogram) reduced the pulmonary vasoconstrictor and bronchoconstrictor responses to hypoxic breathing.
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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 mug/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 mug/ml and appeared to be nearly maximal at 2.0 mug/ml. VIP (100 mug/ml) stimulated adenylate cyclase activity in a membrane preparation from rabbit ileal mucosa. Secretin (6.0 x 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 mug/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 mug/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-mug/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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An octacosapeptide with the entire sequence proposed for the newly isolated vasoactive intestinal polypeptide was synthesized and had the expected biological properties. Synthetic peptides corresponding to the C-terminal hendeca-, tetradeca-, pentadeca-, and docosapeptide sequences of the vasoactive intestinal polypeptide showed activities that increased with increasing chain length.
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A polypeptide, which has potent and diverse biological action-including systemic vasodilation, hypotension, increased cardiac output, respiratory stimulation, and hyperglycemia-was isolated from the small intestine of the hog. The peptide has 28 amino acid residues and is chemically distinct from the kinins, "substance P," glucagon, and secretin.
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