Vasoactive intestinal polypeptide (VIP)-like immunoreactivity in anuran intestine

Summary Immunocytochemical and radioimmunological techniques with region specific antisera have been used to identify a vasoactive intestinal polypeptide-like material in the anuran intestine. Seven species of Anura were investigated: Bombina bombina, Alytes obstetricans, Rana temporaria, Rana esculenta, Hyla arborea, Hyla crepitans and Bufo bufo.In five of the species (A. obstetricans, R. temporaria, H. arborea, H. crepitans and B. bufo) vasoactive intestinal polypeptide-like immunoreactive mucosal endocrine cells and nerve fibres in all layers of the gut wall, were detected by both immunofluorescence and peroxidase-antiperoxidase methods. In the other two species, R. esculenta and B. bombina, no mucosal endocrine cells were detected although the vasoactive intestinal polypeptide-immunoreactive nerve fibres were plentiful.Radioimmunoassay showed the presence of significant amounts of vasoactive intestinal polypeptide-immunoreactivity in intestinal extracts from all species. The highest quantities were present in those anurans with both immunostained cells and nerves. Gel permeation chromatography showed that most of the vasoactive intestinal polypeptide-like peptide eluted in a position identical to that of natural mammalian (porcine) vasoactive intestinal polypeptide.The results indicate that a vasoactive intestinal polypeptide-like peptide is well represented in the Anura and that it is immunologically very similar to the mammalian peptide.Part of this work was presented at the European Society of Comparative Endocrinology, 1979; see Buchan et al. 1980a     

Vasoactive intestinal peptide (VIP)-like immunoreactivity in the human sympathetic ganglia

Vasoactive intestinal peptide immunoreactive (VIP-IR) nerve fibres and terminals, neurons and small granule containing cells were observed in human lumbal sympathetic ganglia. Electron-microscopically VIP-IR was localized in the large dense-cored vesicles in nerve terminals and on the membranes of the Golgi complexes in the neurons. A small population of principal ganglion cells was surrounded by VIP-IR nerve terminals. Most of these neurons contained acetylcholinesterase (AChE) enzyme but were not tyrosine hydroxylase-immunoreactive (TH-IR). All VIP-IR ganglion cells and most of the nerve fibres contained AChE but not TH-IR. It appears that in human sympathetic ganglia VIP is localized in the cholinergic neurons and nerve fibres and that the VIP-IR nerve terminals innervate mainly the cholinergic subpopulation of the sympathetic neurons.     

Vasoactive intestinal peptide (VIP)-like immunoreactivity in the human sympathetic ganglia

Summary Vasoactive intestinal peptide immunoreactive (VIP-IR) nerve fibres and terminals, neurons and small granule containing cells were observed in human lumbal sympathetic ganglia. Electron-microscopically VIP-IR was localized in the large dense-cored vesicles in nerve terminals and on the membranes of the Golgi complexes in the neurons. A small population of principal ganglion cells was surrounded by VIP-IR nerve terminals. Most of these neurons contained acetycholinesterase (AChE) enzyme but were not tyrosine hydroxylase-immnoreactive (TH-IR). All VIP-IR ganglion cells and most of the nerve fibres contained AChE but not TH-IR. It appears that in human sympathetic ganglia VIP is localized in the cholingergic neurons and nerve fibres and that the VIP-IR nerve terminals innervate mainly the cholinergic subpopulation of the sympathetic neurons.     

Vasoactive intestinal polypeptide (VIP) immunoreactivity of endocrine-like cells in the feline pyloric mucosa

Summary Immunoreactivity to VIP by endocrine-like cells in the feline pyloric mucosa was examined by using three kinds of region-specific anti-porcine VIP sera. VIP-immunoreactive endocrine-like cells were detected clearly with all of the VIP antisera used. They were located mainly around the neck of the pyloric glands. Some of these endocrine-like cells showed dilution-dependent immunoreactivity against VIP antisera. The immunostaining intensity of VIP-immunoreactive endocrine-like cells showing dilution-independence could not be distinguished from those of nerve elements. The present results suggest that the immunoreactivity with properties very similar to those of authentic VIP may be present in the endocrine-like cells of the feline pyloric glands.     

Vasoactive intestinal polypeptide (VIP): current status

Research on VIP continues at a rapid pace. Recent progress includes: insights into its biosynthesis (and that of a closely related PHI-like peptide) and its neuronal localization, discovery of novel biological actions, new data on its release and binding to specific receptors, and additional evidence for its roles in physiological regulation and in the pathogenesis of disease.     

Vasoactive intestinal polypeptide (VIP) provokes vaginal lubrication in normal women

The human vagina is known to be heavily innervated by vasoactive intestinal polypeptide (VIP) immunoreactive nerve fibres. In the present study we have examined the effect of VIP (900 pmol x kg-1 x h-1, IV during 30 min) on vaginal lubrication and blood flow in fourteen normal non-pregnant women. Vaginal blood flow was measured by the heat clearance technique and the vaginal lubrication quantified by the weight gain of preweighed filter papers placed on the surface of the vaginal wall for 30 min. Arterial blood pressure, pulse frequency and the concentration of VIP in peripheral blood were monitored. VIP (median concentrations of 200-300 pmol x l-1) induced a significant increase in vaginal blood flow accompanied by a 100% increase in vaginal lubrication (from 27 mg/cm2 to 53 mg/cm2). The VIP infusion lead to a significant increase in pulse frequency and a significant fall in diastolic arterial blood pressure. The findings suggest that VIP may participate in the control of the local physiological changes observed during sexual arousal: genital vasodilation and increase in vaginal lubrication.     

Vasoactive intestinal polypeptide (VIP) as a putative neurotransmitter in penile erection

The localization of vasoactive intestinal polypeptide (VIP) in the male genitourinary tract was investigated in the rabbit and man by means of radioimmunoassay and immunohistochemistry. In addition, the in vitro effect of VIP upon penile smooth muscle from man, the Vervet monkey, and the rabbit was investigated. Significant concentrations of VIP immunoreactivity were found in the human penis and all the organs of the rabbit genital tract apart from the testis. VIP immunoreactive nerve fibres were observed in the erectile tissue of the human and rabbit penis and in the other organs of the rabbit genital tract apart from the testis. Fibres were most abundant in association with blood vessels, in smooth muscle tissue, and subepithelially in glandular tissue. Strips of smooth muscle taken from the corpus cavernosum of Vervet monkey and man showed a dose-dependent relaxation in response to VIP at concentrations of 6 X 10(-8) mol X L-1 and 6 X 10(-7) mol X L-1. The data indicate that VIP may be an inhibitory neurotransmitter involved in the nervous control of penile erection.     

Vasoactive intestinal polypeptide (VIP) inhibits rat alveolar macrophage phagocytosis and chemotaxis in vitro.

Vasoactive intestinal polypeptide (VIP) has been shown to inhibit lymphocyte function and is believed to modulate the immune response. We explored the possible immunomodulatory effects of VIP on alveolar macrophage (AM) function by examining its influence on AM phagocytosis and chemotaxis. Rat AMs were collected by bronchoalveolar lavage and incubated for 90 min with polystyrene beads in the presence or absence of VIP in concentrations from 10(-11) M to 10(-5) M. VIP significantly (P less than 0.0001) inhibited AM phagocytosis of polystyrene beads at concentrations of 10(-11) to 10(-6) M, with a maximal inhibition of 35% at 10(-6) M (but no inhibition at 10(-5) M). AMs were also incubated for 90 min in a chemotaxis chamber with endotoxin-activated rat serum (EARS) as a chemoattractant, with or without VIP in concentrations from 10(-9) to 10(-6) M. VIP significantly (P less than 0.0001) inhibited AM chemotaxis by at least 30% at concentrations of 10(-9) to 10(-6) M, with a maximal inhibition of 46% at 10(-7) M. These results indicate that VIP, in concentrations from 10(-11) to 10(-6) M, inhibits rat AM function as assessed by phagocytosis of polystyrene beads and chemotaxis to EARS. The inhibition of alveolar macrophage function is another mechanism by which VIP may modulate the immune response in the lung.     

Vasoactive intestinal polypeptide (VIP) as a cholinergic co-transmitter: some recent results

The neuropeptide vasoactive intestinal polypeptide (VIP) copurifies with mammalian brain cholinergic synaptosomes when these are separated from the total brain synaptosome fraction by an immunoadsorption procedure based on an antiserum to a cholinergic-specific antigen. VIP must therefore be reckoned to be a cholinergic co-transmitter in brain. In electromotor and myenteric neurones the two transmitters are differently packaged. The frequency-dependence and pharmacology of release show that the intracellular dynamics of the storage and release processes are quite different for the two neurotransmitters. However in the ileum a portion of the vesicle-bound acetylcholine is recovered in the VIP-storing particles and this might indicate a precursor-product relationship for the two types of vesicle in this system analogous to that which has been proposed for electron-dense and electron-translucent vesicles in noradrenergic nerves.     

Vasoactive intestinal polypeptide (VIP) stimulates adenylate cyclase in selected areas of rat brain

VIP stimulated adenylate cyclase activity in homogenates of some areas of rat brain that are rich in this peptide, e.g., cerebral cortex, hypothalamus and hippocampus, as well as in cerebellar cortex, where VIP content is low. No stimulation occurred in caudate nucleus or brainstem. The enzyme stimulation was inhibited by Ca²⁺, but unaffected by guanine nucleotides. Synthetic fragments of VIP (VIP_6?28 & VIP_14–28) neither stimulated cyclase activity nor inhibited VIP-induced stimulation.     

Vasoactive intestinal peptide (VIP) stimulates aldosterone secretion by rat adrenal glands in vivo

VIP acutely enhanced the plasma concentration of aldosterone (but not that of corticosterone) both in normal rats, and in rats chronically treated with dexamethasone and ACTH or captopril and angiotensin II. VIP increased aldosterone blood concentration in chronically captopril-treated animals, but not in rats in which ACTH secretion was inhibited by dexamethasone. These findings suggest that VIP is specifically involved in the stimulation of the secretory activity of rat zona glomerulosa, and that this action of VIP requires a normal level of circulating ACTH.     

Cellular localization and ontogeny of immunoreactive Vasoactive intestinal polypeptide (VIP) in the chicken gut

Summary Vasoactive intestinal polypeptide (VIP)-immunoreactive nerves were abundant along the entire digestive tract of the chicken. In the proventriculus, gizzard and small intestine VIP nerves were numerous around glands and less numerous in the smooth muscle. Submucosal blood vessels were often encircled by VIP nerves. VIP nerves were also seen in the submucosal and myenteric plexus. In the large intestines the VIP innervation of the smooth muscle was more predominant, while there was a rather sparse supply of VIP nerves around the base of the crypts. This innervation pattern was a consistent finding with four different VIP antisera. VIP-immunoreactive cells, however, were demonstrated with only three of the antisera. They were found scattered in the epithelium of the proventriculus and small and large intestines. The failure of one of the antisera to demonstrate endocrine cells suggests that the VIP-immunoreactive material in these cells differs from that in nerves. Conceivably, the material present in nerves represents VIP, while that in endocrine cells represents cross-reacting peptides or other molecular forms of VIP.VIP nerves appeared comparatively early in embryonic development. They appeared in the upper part of the digestive tract at 13 days of incubation and in the colon a few days before hatching; at this stage, only smooth muscle received VIP nerves. The adult pattern of innervation was established about two to four weeks after hatching. VIP-immunoreactive endocrine cells appeared in the intestines a few days before hatching. The adult frequency of occurrence was established about one week after hatching.     

Functional vasoactive intestinal polypeptide (VIP)-system in salt glands of the Pekin duck

Summary In saltwater-acclimated ducks with fully specialized supraorbital salt glands, intracarotid application of acetylcholine (5 nmoles/min/kg b.w.) or porcine vasoactive intestinal polypeptide (pVIP) (240 pmoles/min/kg b.w.) induced secretion from the salt glands at threshold conditions of secretory activity. pVIP-like immunoreactivity could be localized in fibers of the postganglionic secretory nerve ramifying throughout the glandular parenchyma. Both middle-sized arterioles and secretory tubules were innervated, and pVIP-immunoreactive varicose fibers formed peritubular baskets around the basal region of secretory tubules indicating direct innervation of the secretory tissue. pVIP-specific staining could be abolished by preabsorption of the antiserum with peptide extracts of salt-gland tissue. Synthetic pVIP and endogenous VIP from salt glands of the duck co-eluted on the HPLC system, suggesting structural similarity of the peptides. Membrane-binding studies with radioiodinated pVIP revealed the presence of high-affinity binding sites in salt-gland tissue. Affinities of unlabeled pVIP analogues to compete for these binding sites were as follows: pVIP > PHI > pVIP antagonist > secretin > pVIP (10–28) > chicken VIP (16–28). Peptide extracts of salt glands had affinities similar to pVIP. Binding sites could be localized mainly at the apical end of the radially arranged secretory tubules, as demonstrated by receptor autoradiography.It is concluded that, in addition to the classical parasympathetic transmitter acetycholine, VIP serves as neuromodulator/transmitter in cranial parasympathetic control of avian salt-gland secretion by acting on both the arteriolar network and the secretory tubules of the gland.     

Vasoactive intestinal peptide (VIP): an amnestic neuropeptide

Vasoactive intestinal peptide (VIP) is a neuropeptide present in high concentrations in the hippocampus. The studies reported here demonstrate that VIP administered into the third ventricle of the brain caused amnesia in mice trained on a left-right footshock avoidance task in a T-maze. VIP resulted in amnesia when administered directly into the rostral portion of the hippocampus at a 10-fold lower dose than was needed to produce amnesia when VIP was administered intracerebroventricularly. When VIP was administered 24 hr after training, it failed to impair retention measured a week later. VIP receptor antagonist ([4-Cl-D-Phe6,Leu17]VIP) enhanced retention when administered into the rostral portion of the hippocampus, suggesting that VIP plays a physiological role in memory modulation. VIP receptor antagonist administered 24 hr after training did not facilitate retention. To gain some insight as to how VIP may be affecting memory processing, we determined if some memory-improving compounds showed a selective ability to block amnesia induced by VIP. The amnestic effect of VIP was blocked by peripheral administration of the memory-enhancing agents, arecoline, naloxone and ST 587 (a noradrenergic receptor agonist) but not by cholecystokinin octapeptide. Central administration of arecoline, but not neuropeptide Y, blocked the amnestic effect of VIP. It is concluded that VIP is a potent amnestic peptide.     

Vasoactive intestinal polypeptide (VIP) inhibits neurally evoked smooth muscle activity of rat uterine cervix in vitro

VIP inhibits the spontaneous motor activity (including tone) in isolated preparations of uterine cervix from oophorectomized rats, but has no direct effect on preparations from estrogen-treated animals. Electrical field stimulation of nerves in the tissue evokes a contractile response that is inhibited by VIP in a concentration-dependent manner. The neuronal link probably involves a cholinergic mechanism, since the contraction is blocked by atropine. The results suggest the presence of VIP receptors both in cholinergic nerves and in smooth muscle cells of the rat uterine cervix.     

Vasoactive intestinal polypeptide immunoreactivity in the spinal cord of the guinea pig

Summary The distribution of vasoactive intestinal polypeptide-immunoreactive (VIP-IR) neurons in the lower medulla oblongata and the spinal cord has been analyzed in guinea pigs. This study includes results obtained by colchicine treatment and transection experiments. In the spinal cord, numerous VIP-IR varicosities were observed in the substantia gelatinosa of the columna dorsalis; some were also found in the substantia intermedia and the columna anterior. The spinal VIP-IR nerve fibers were mainly of intraspinal origin and oriented segmentally. VIP-IR nuclei in the spinal cord extended dorsally into corresponding regions of the caudal medulla oblongata, namely from the substantia intermedia medialis and lateralis into the vagus-solitarius complex and from the nucleus spinalis lateralis into the area of the nucleus reticularis lateralis. Additional VIP-IR perikarya were observed in the pars caudalis of the nucleus spinalis nervi trigemini. The VIP-IR nuclei within the caudal medulla oblongata probably form a continuous system with those localized within the spinal cord. They may be involved functionally in the modulation of cardiovascular and respiratory regulation in the guinea pig.Supported by the DFG, Carvas SFB 90     

Vasoactive intestinal peptide (VIP) receptors in the canine gastrointestinal tract

Vasoactive intestinal peptide (VIP) is a putative neurotransmitter in both the brain and peripheral tissues. To define possible target tissues of VIP we have used quantitative receptor autoradiography to localize and quantify the distribution of ¹²⁵I-VIP receptor binding sites in the canine gastrointestinal tract. While the distribution of VIP binding sites was different for each segment examined, specific VIP binding sites were localized to the mucosa, the muscularis mucosa, the smooth muscle of submucosal arterioles, lymph nodules, and the circular and longitudinal smooth muscle of the muscularis externa. These results identify putative target tissues of VIP action in the canine gastrointestinal tract. In correlation with physiological data, VIP sites appear to be involved in the regulation of a variety of gastrointestinal functions including epithelial ion transport, gastric secretion, hemodynamic regulation, immune response, esophageal, gastric and intestinal motility.     

Vasoactive intestinal peptide (VIP) cells in the pancreas and gastro-intestinal mucosa

Summary Using antibodies against pure porcine VIP in immunoperoxidase and immunofluorescence tests, VIP-immunoreactive cells have been detected in the pancreas—especially in the islets—and gastrointestinal mucosa of the dog, guinea-pig and man. VIP immunoreactive cells were widely distributed in these tissues, never being numerous at any site. Some parallelism has been noted between such cells and ultrastructurally identified D₁ cells of the pancreas and gastrointestinal mucosa. The presence of VIP cells in normal pancreas may help explain the occurrence of pancreatic endocrine tumors producing VIP.