VIP suppression in the intestine and cerebral cortex following administration of VIP antiserum to newborn rats.

The administration of vasoactive intestinal peptide (VIP) antiserum to newborn rats significantly reduced the VIP content, both in the cerebral cortex and in intestinal epithelial cells. The decrease was observed at postnatal days 14 and 21 and also in 90 day-old animals. The neonatal treatment produced a significant increase in the density of high- and low-affinity binding sites for VIP in the cerebral cortex at post-natal days 14 and 21 whereas in the intestinal epithelial cells only the low-affinity binding sites were up-regulated at the same time points. VIP suppression induced by neonatal administration of the corresponding antiserum may represent a useful approach to further characterize the physiological role of this neuropeptide.

Effects of sensitization on vasoactive intestinal polypeptide-induced relaxation and its concentration and binding in guinea-pig airways.

We investigated the relaxant effect of vasoactive intestinal polypeptide (VIP) in trachea and lung parenchyma from normal and sensitized guinea-pigs. A technique by which drug access was restricted to either the mucosal or the adventitial surface of tracheal rings was used. In intact trachea, concentration-response curves for VIP entering from the mucosal surface (pD2 = 6.61 +/- 0.06) were displaced to the right compared with those for adventitial entry (pD2 = 6.78 +/- 0.04). Epithelium removal produced a leftward shift (approximately 2.8-fold) in the mucosal VIP concentration-response curve. Sensitization did not alter the responsiveness (maximal effect) or sensitivity (pD2 values) of tracheal rings to VIP irrespective of the surface of drug entry and of the absence or presence of epithelium. VIP-induced relaxation of normal and sensitized lung strips was also similar. Sensitization resulted in a significant decrease in tracheal VIP content (from 2.16 +/- 0.07 in normal to 0.60 +/- 0.08 nmol/mg protein in sensitized trachea; P < 0.05; n = 7) whereas the affinity of both high- and low-affinity binding sites for VIP increased as compared to that of normal trachea. Differences were not found in the binding capacities of normal and sensitized trachea. VIP content and binding did not differ in normal and sensitized lung. In conclusion, immunological sensitization produced changes in VIP tracheal content and binding but neither VIP-induced relaxation of isolated airways nor the influence of epithelium in this response was altered.

The vasoactive intestinal peptide receptor-effector system is developmentally regulated in rat jejuno-ileal epithelial cells.

The specific binding of vasoactive intestinal peptide (VIP) to its specific receptors as well as the stimulatory effect of the neuropeptide on cyclic AMP accumulation were studied in jejuno-ileal epithelial cells from 14-, 20- and 60-day-old rats. The potency and specificity of the VIP receptor-effector system did not vary during development. However, the concentration of VIP receptors and the efficiency of VIP stimulation of cyclic AMP generation increased from suckling to adult conditions, and VIP levels in jejuno-ileal tissue followed a parallel course.

Interaction of insulin with small intestinal epithelial cells from developing rats.

The interaction of insulin with its specific receptors was studied in jejunoileal epithelial cells from 14-, 20-, and 60-day-old rats. Characteristics such as potency and specificity of the insulin receptor system did not vary during development. However, insulin binding decreased with age due to a diminished concentration of insulin receptors, whereas the circulating levels of the hormone followed an inverse evolution. These results support previous suggestions on the potential role of insulin on the mechanisms of differentiation and proliferation of small intestinal mucosa.

VIP interaction with intestinal epithelial cells and liver plasma membranes from hepatectomized rats.

Specific binding of VIP and VIP-stimulated cyclic AMP accumulation were studied in jejuno-ileal (villous and crypt) and colonic epithelial cells three days after partial (70%) hepatectomy in the rat. The binding capacity (but not the affinity) of VIP receptors, and the efficiency (but not the potency) of VIP on cyclic AMP stimulation increased after hepatectomy (as compared to sham-operated rats). On the other hand, the affinity (but not the binding capacity) of VIP receptors in plasma membranes of the regenerating liver was decreased as compared to the control condition. The possibility that these findings may be related to an involvement of VIP in hepatic growth regulation deserves further investigation.

Interaction of vasoactive intestinal peptide with rat small intestinal epithelial cells after intestinal resection.

Specific binding of vasoactive intestinal peptide (VIP) and VIP-stimulated cyclic AMP accumulation were studied in small intestinal epithelial cells (both of crypt and villous levels) 3, 7 and 14 d after a 60% resection of the small intestine. The affinity, but not the binding capacity, of VIP receptors decreased during the adaptive hyperplastic response. Basal cyclic AMP levels were similar in cells of both control and resected rats. Resection induced a decrease of potency, but not of efficiency, of VIP on the stimulation of cyclic AMP accumulation.

Effect of resection of small intestine on the interaction of vasoactive intestinal peptide with rat colonic epithelial cells.

Vasoactive intestinal peptide (VIP) receptors and VIP-dependent cyclic AMP production were studied in rat colonic epithelial cells 3 days after a 60% resection of the small intestine. Basal cyclic AMP levels were similar in both control and resected animals. The potency, but not the efficiency, of the peptide on the stimulation of cyclic AMP production was diminished in cells from resected rats. Accordingly, the affinity of VIP receptors, but not the binding capacity, decreased as a consequence of the loss of a part of the small intestinal mucosa. These observations are consistent with the known inhibitory role of cyclic AMP on cell proliferation in colonic epithelium and other tissues and suggest a participation of VIP acting through the cyclic nucleotide in the compensatory hyperproliferative response of the colon following massive resection of the small intestine.

Influence of ligation of pancreatic and bile ducts on the interaction of vasoactive intestinal peptide with rat duodenal epithelial cells.

The specific binding of vasoactive intestinal peptide (VIP) and the stimulatory effect of the neuropeptide on cyclic AMP in duodenal epithelial cells were modified 3 days following pancreaticobiliary exclusion. The binding capacity, but not the affinity, of VIP receptors decreased (by about 50%) as a consequence of the surgical manipulation. VIP was equally potent but showed a lower efficiency (about 45%) in stimulating cyclic AMP after ligation of the pancreatic and bile ducts. These observations may be either a consequence or a cause of the adaptive response of duodenal epithelium, the last possibility suggesting a role of VIP in the mechanisms of growth and differentiation of intestinal mucosa.