Vasoactive intestinal peptide (VIP): specific receptors and adenylate cyclase activation in a human prolactin-secreting pituitary tumor]

Receptors for the Vasoactive Intestinal Peptide (VIP) were characterized in particles enriched in plasma membranes obtained from a human prolactin-secreting pituiatry tumor. Native VIP inhibited competitively the binding of 125I-VIP to the particles and stimulated cyclic AMP production; both these effects were observed at concentrations of VIP as low as 10(-11)-10(-10) M, which are compatible with VIP concentrations in the hypothalamopituitary portal blood.     

Receptors for vasoactic intestinal peptide (VIP) in human colonic adenocarcinoma membranes: specific binding and stimulation of adenylate cyclase]

Human colonic adenocarcinoma plasma membranes exhibit specific receptors for VIP. Adenylate cyclase activity is stimulated by a VIP concentration as low as 10(-10) mol/1.     

A glucagon-secretin-like peptide stimulates the intrinsic nervous plexus of guinea pig gallbladder

The role of vasoactive intestinal peptide (VIP), as a possible neurotransmitter of the intrinsic nerve plexus in the guinea pig gallbladder, was investigated by monitoring spontaneous contractile activity. VIP receptor antagonist (4 Cl-D-Phe6, Leu 17)-VIP did not produce any effect on muscular tone and spontaneous activity, whereas (N-Ac-Tyr1, D-Phe2)-GRF-(1-29)-NH2, (14-GRF analog), which is known to stimulate digestive enzyme secretion by interacting with the VIP-preferring receptors, greatly increased the amplitude and frequency of waves as well as the muscular tone. Since VIP receptor antagonist acts selectively as a competitive antagonist for the action of VIP, we conclude that the gallbladder inhibitory intrinsic plexus neurotransmitter is not VIP, but a member of the glucagon-secretin family of peptides.     

A glucagon-secretin-like peptide stimulates the intrinsic nervous plexus of guinea pig gallbladder

Summary The role of vasoactive intestinal peptide (VIP), as a possible neurotransmitter of the intrinsic nerve plexus in the guinea pig gallbladder, was investigated by monitoring spontaneous contractile activity. VIP receptor antagonist (4 Cl-D-Phe⁶, Leu¹⁷)-VIP did not produce any effect on muscular tone and spontaneous activity, whereas (N-Ac-Tyr¹, D-Phe²)-GRF-(1-29)-NH₂, (14-GRF analog), which is known to stimulate digestive enzyme secretion by interacting with the VIP-preferring receptors, greatly increased the amplitude and frequency of waves as well as the muscular tone. Since VIP receptor antagonist acts selectively as a competitive antagonist for the action of VIP, we conclude that the gallbladder inhibitory intrinsic plexus neurotransmitter is not VIP, but a member of the glucagon-secretin family of peptides.     

Secretion of insulin and of glucagon by the perfused pancreas of newborn rats: effect of vasoactive intestinal peptide Vip]

A method is described for perifusion of the splenic part of the pancreas from 48-64 hour-old rat. In different basal conditions, the secretion of insulin and glucagon is stable and reproducible for 90 mn. The addition of the vasoactive intestinal peptide (VIP) to these perifusion media, at a concentration as low as 2 ng/ml, determines a remarkable increase of insulin and of glucagon secretion. These results suggest the possibility of a VIP action in the physiology of endocrine pancreas.     

Direct evidence for pH-dependent Fc receptors on proximal enterocytes of suckling rat gut.

By means of an erythrocyte-antibody rosette technique, Fc receptors, functional at pH 6.0 but not at 7.2, were shown to be present on enterocytes isolated from duodenum and jejunum (but absent from ileum) of 12-20-day-old suckling rats.     

Priming effect of vasoactive intestinal peptide on the respiratory burst of neutrophils non-mediated by plasma membrane receptors

Vasoactive intestinal peptide (VIP) primed the respiratory burst of human neutrophils in response to phorbol myristate acetate. Maximal and half-maximal effects were achieved at 10 and 0.5 nM VIP respectively. The absence of plasma membrane receptors to VIP in neutrophils suggests that priming of the respiratory burst should be considered as a side effect of VIP. However, from the above indicated concentration range, the priming of the neutrophil by VIP cannot be considered as a pharmacological effect. The enhancement of the formation of reactive oxygen metabolites by VIP may be important in the pathology of VIP-producing tissues.     

Role of phospholipids in the binding activity of vasoactive intestinal peptide receptors

Phospholipase digestion of rat intestinal epithelial cell membranes was performed in order to study the influence of membrane phospholipids on the binding activity of VIP receptors. Phospholipases A2 and C strongly (ED50 congruent to 4 X 10(-2) and 4 X 10(-1) micrograms/ml, respectively) and rapidly reduced 125I-VIP binding to membranes whereas phospholipase D was ineffective. This suggests an important role of both hydrophobic and hydrophilic groups of phospholipids on VIP receptor binding activity.     

Interaction of vasoactive intestinal peptide (VIP) with cholinergic stimulation of glucagon secretion

Summary VIP-containing nerve fibers as well as cholinergic nerve fibers have a ubiquitous distribution in the body and both types of nerves have been demonstrated to innervate the pancreatic islets. The present study shows, in the intact, conscious mouse, that VIP and the cholinergic agonist carbachol stimulate glucagon secretion in a dose-dependent manner. Furthermore VIP and carbachol were found to exert potentiating interactions on glucagon secretion. These results suggest the existence of an interactive neural regulation of glucagon secretion, exerted by acetylcholine and VIP.We thank Professor V. Mutt, Karolinska Institutet, Stockholm, for giving us VIP. The skilful technical assistance of Lena K vist and Peter Okmark is gratefully acknowledged. This study was supported by grants from the Swedish Medical Research Council (14P-4289, 14X-4286) and the Medical Faculty, University of Lund, Sweden.     

Somatostatin and 3-oxy-methyl-D-glucose (3-OMG) uptake in isolated chicken intestinal epithelial cells

The direct effect of somatostatin on the absorption of 3-oxymethylglucose in epithelial cells isolated from the small intestine of chicken was studied. The presence of somatostatin in the incubation medium at concentrations of 3.5 X 10(-8) M and 7 X 10(-8) M produced significant dose-dependent increases in the accumulation of sugar in the enterocytes. This effect might be due to an increase in the cell membrane permeability caused by hormone action.     

Dsg2 via Src-mediated transactivation shapes EGFR signaling towards cell adhesion

Rapidly renewing epithelial tissues such as the intestinal epithelium require precise tuning of intercellular adhesion and proliferation to preserve barrier integrity. Here, we provide evidence that desmoglein 2 (Dsg2), an adhesion molecule of desmosomes, controls cell adhesion and proliferation via epidermal growth factor receptor (EGFR) signaling. Dsg2 is required for EGFR localization at intercellular junctions as well as for Src-mediated EGFR activation. Src binds to EGFR and is required for localization of EGFR and Dsg2 to cell–cell contacts. EGFR is critical for cell adhesion and barrier recovery. In line with this, Dsg2-deficient enterocytes display impaired barrier properties and increased cell proliferation. Mechanistically, Dsg2 directly interacts with EGFR and undergoes heterotypic-binding events on the surface of living enterocytes via its extracellular domain as revealed by atomic force microscopy. Thus, our study reveals a new mechanism by which Dsg2 via Src shapes EGFR function towards cell adhesion.     

Vasoactive intestinal peptide (VIP) occurs in nerves of the pineal gland

Summary Nerves staining with antibodies against vasoactive intestinal peptide (VIP) were detected in the pineal gland of the rabbit, cat and pig. VIP nerves were numerous in the cat but few in the rabbit and pig. A particularly rich VIP nerve supply was noted in the pineal stalk of the cat. The nerves were predominantly located around small blood vessels. Occasionally, nerve fibres were seen in the glandular parenchyma without obvious relation to blood vessels.Grant support from the Swedish Medical Research Council (04X-4499).     

VIP and histamine H2 receptor activity in human fetal gastric glands

Vasoactive intestinal peptide (VIP, EC50 = 6.4 X 10(-10)M) and histamine (EC50 = 3 X 10(-6)M) activated the cyclic AMP generating system in gastric glands isolated from two human fetuses at 23 weeks gestation. Histamine antagonism by the H2 receptor blockers cimetidine (Ki = 0.35 X 10(-6)M) and ranitidine (ki = 0.51 X 10(-7)M) clearly characterized the histaminic activation as being of the H2 type. It is suggested that these two vasoactive hormones may operate as neurocrine/paracrine regulators of the differentiation and/or function of the human gastric mucosa in utero.     

Changes in the concentration of vasoactive intestinal peptide in intestinal lymph in response to vagal stimulation in the calf

Summary Stimulation of both vagi caused a significant rise in arterial plasma vasoactive intestinal peptide (VIP) concentration in 3–5-week-old calves with cut splanchnic nerves. This was associated with a pronounced rise in the VIP concentration of intestinal lymph showing that vagal stimulation causes release of VIP from splanchnic viscera.Acknowledgment. This work has been supported by grants from the Agricultural Research Council and the Medical Research Council and we are indebted to Dr D.M. Burley (CIBA) for his continued support.     

Relationship of phosphatidylcholine to hydrophobic surfactant on rat intestinal chylomicron secretion

Hydrophobic surfactants such as Poloxalene inhibit triglyceride secretion into lymph by enterocytes. The inhibitory effect of these agents on triglyceride secretion is reversed when lipid presented for absorption is exclusively in the form of phosphatidylcholine (PC) and not triglyceride. The present investigation performed in conscious mesenteric lymph fistula rats was designed to determine whether various mixtures of triglyceride and PC given intraduodenally with Poloxalene would also reverse the inhibitory effect of Poloxalene on triglyceride secretion into lymph. A 50–50 mixture of triolein (TO) and PC resulted in normal triglyceride secretion into lymph. However, when the mixture of lipids was 75-25, TO to PC, results for triglyceride recovery in lymph were considerably reduced. The transport rate for triglyceride into lymph was not as depressed, however, as observed for Poloxalene treated rats given lipid for absorption basically in the triglyceride form. Substitution of phosphatidylethanolamine for PC had no beneficial effect on triglyceride secretion in Poloxalene treated rats. It is concluded that PC can reverse the inhibitory effect of Poloxalene on triglyceride secretion into lymph even when considerable amounts of triglyceride along with PC are presented for absorption.     

Peptide-stimulated release of prolactin from the fowl anterior pituitary gland

Summary Anterior pituitary glands from broiler fowl were preincubated for 24 h in either medium 199 only or medium containing estradiol 17, following which they were incubated in medium containing thyrotrophin releasing hormone (TRH), vasoactive intestinal polypeptide (VIP) or substance P (SP), alone or with the dopamine agonist, apomorphine. Estradiol priming stimulated release of prolactin and enhanced apomorphine-inhibition of prolactin release. TRH stimulated prolactin release, an effect reversed by apomorphine, and priming with estradiol potentiated both effects. VIP stimulated prolactin to a lesser degree and again this was inhibited by apomorphine and potentiated by estradiol. SP had little effect on the nonsteroid-primed pituitary, but stimulated release of prolactin after estradiol treatment, though less effectively than TRH or VIP.     

Nerve-mediated action of forskolin on guinea pig ileal mucosa

The effects of forskolin on myenteric neuronal activity and mucosal function were examined in guinea pig ileum. Forskolin increased the excitability of myenteric neurons, and increased mucosal chloride secretion by stimulating enteric neurons as well as by acting directly on enterocytes.     

Direct evidence for pH-dependent Fc receptors on proximal enterocytes of suckling rat gut

Summary By means of an erythrocyte-antibody rosette technique, Fc receptors, functional at pH 6.0 but not at 7.2, were shown to be present on enterocytes isolated from duodenum and jejunum (but absent from ileum) of 12–20-day-old suckling rats.     

Glycogenolytic effect of vasoactive intestinal peptide in the rat in vivo

Summary The effects of VIP (300 pmol/kg), injected via the portal vein, on the glycogen content of the liver and on glycemia, were studied in the rat in vivo. VIP enhanced glycogenolysis and caused hyperglycemia in a time-dependent manner.     

Selective effects of PHA on rat brush border hydrolases along the crypt-villus axis

The mechanism of the toxicity of lectin from Phaseolus vulgaris seeds has been investigated on rat enterocytes. Cell isolation procedures showed a selectivity in the loss of brush border hydrolases; this indicated that the microvilli blebbing was not the only mechanism of action of lectins on rat enterocytes.