Quantitative studies of vasoactive intestinal peptide (VIP) binding sites and VIP-induced adenosine 3':5'-monophosphate production in epithelial cells from duodenum, jejunum, ileum, cecum, colon and rectum in the rat

Abstract

The binding of vasoactive intestinal peptide (VIP) and its effect on adenosine 3':5'-monophosphate (cyclic AMP) production were measured in isolated rat intestinal epithelial cells from duodenum, jejunum ileum, cecum, colon and rectum. In every segment tested, VIP binding and VIP-induced cyclic AMP production exhibited a similar pattern with two populations of VIP binding sites and similar magnitude of cyclic AMP production. Continuous displacement of the binding of 125I-labelled VIP and stimulation of cyclic AMP production were observed in the range of 10(-10)--10(-7) M VIP concentrations. Fifty per cent inhibition of the initial binding of tracer was obtained with 2.2 to 3.2 nM VIP. The Km of stimulation of cyclic AMP production was 1.2 to 2.6 nM VIP. Chicken VIP and porcine secretin showed a 4-fold higher and a 100-fold lower affinity than porcine VIP for binding sites, respectively. The same was true for the stimulation of cyclic AMP production. The existence of receptors highly sensitive to VIP in the separate segments of the bowel corresponds to the presence of high concentration of VIP at the vicinity of epithelial cells and strongly suggests that VIP is active in regulating different intestinal functions.