Involvement Of Vasoactive Intestinal Polypeptide Research Articles

The role of vasoactive intestinal peptide (VIP) in atropine-related inhibition of the progression of myopia

ObjectiveThis study aimed to investigate the potential involvement of vasoactive intestinal polypeptide (VIP) in myopia development and its contribution to the mechanism of action of the anti-myopia drug, atropine.MethodsThirty-three-week-old guinea pigs were randomly divided into normal control (NC, n = 10), monocularly form-deprived (FDM, n = 10), and FDM treated with 1% atropine (FDM + AT, n = 10) groups. The diopter and axial length were measured at 0, 2, and 4 weeks. Guinea pig eyeballs were removed at week four, fixed, and stained for morphological changes. Immunohistochemistry (IHC) and in situ hybridization (ISH) were performed to evaluate VIP protein and mRNA levels.ResultsThe FDM group showed an apparent myopic shift compared to the control group. The results of the H&E staining were as follows: the cells of the inner/outer nuclear layers and retinal ganglion cells were disorganized; the choroidal thickness (ChT), blood vessel lumen, and area were decreased; the sclera was thinner, with disordered fibers and increased interfibrillar space. IHC and ISH revealed that VIP's mRNA and protein expressions were significantly up-regulated in the retina of the FDM group. Atropine treatment attenuated FDM-induced myopic shift and fundus changes, considerably reducing VIP's mRNA and protein expressions.ConclusionsThe findings of elevated VIP mRNA and protein levels observed in the FDM group indicate the potential involvement of VIP in the pathogenesis and progression of myopia. The ability of atropine to reduce this phenomenon suggests that this may be one of the molecular mechanisms for atropine to control myopia.

Vasoactive Intestinal Polypeptide as Possible Mediator of Relaxation in the Rat Gastric Fundus

Relaxations were induced in longitudinal muscle strips of the rat gastric fundus by stimulation of non-adrenergic non-cholinergic (NANC) neurons and by administration of vasoactive intestinal polypeptide (VIP) or isoprenaline. The effect of antiserum against vasoactive intestinal polypeptide (VIP antiserum) and of control serum on these relaxations was investigated. Incubation with VIP antiserum (dilution 1/50) for 1 h almost completely prevented the relaxation by VIP. It partially prevented the relaxation evoked by electrical stimulation while the relaxation induced by isoprenaline was not influenced. Control serum decreased the VIP- and stimulation-induced relaxations much less than did VIP antiserum. In addition, the effect of the putative VIP antagonist (4Cl-D-Phe6, Leu17) VIP was studied on the relaxations induced by NANC neuron stimulation and by VIP. The VIP antagonist (3 x 10(-5) M, incubation time 10 min) had a relaxatory effect itself but had no influence on either VIP- or stimulation-induced relaxations. The results with VIP antiserum confirm the involvement of VIP in the inhibitory NANC neurotransmission of the rat gastric fundus.

Expression of vasoactive intestinal polypeptide, substance P and neuropeptide Y in jejunal enteric nerves is altered in rabbits suffering from long term Trichinella spiralis infection: an immunohistochemical study

In the early intestinal stage of infection with the nematode <I>Trichinella spiralis</I> alterations in gut motility and chemical code of enteric neurons are observed. The present study was designed to characterize the changes in expression pattern of vasoactive intestinal polypeptide (VIP), substance P (SP) and neuropeptide Y (NPY) in enteric nerves of the rabbit jejunum occurring during long-lasting trichinellosis (35 and 42 days). Sections of the jejunum from healthy and <I>T. spiralis</I>-infected rabbits were processed for double immunocytochemistry in which antibodies against protein gene product 9.5 were used as a pan-neuronal marker and mixed with antisera raised against VIP, SP or NPY. At 35 and 42 days post infection a marked decrease of VIP-, SP- and NPY-immunoreactive (IR) jejunal myenteric neurons was found, whereas the expression of these neuropeptides in submucous neurons was unchanged. In the myenteric plexus and the jejunal circular muscle of <I>T. spiralis</I>-infected rabbits a significant reduction of VIP-IR (but not SP-IR) nerve fibres was noted. In the longitudinal muscle of the jejunum from animals with long-lasting trichinellosis the density of SP-IR nerve terminals was decreased, whereas the number of VIP-containing nerve fibres was unchanged. Long-lasting trichinellosis had no influence on NPY-IR nerve fibres in both circular and longitudinal smooth muscles. The number of NPY-positive (but not VIP- and SP-IR) nerve fibres supplying mucosa and blood vessels was decreased in <I>T. spiralis</I>-infected animals. These data indicate that during long-lasting trichinellosis expression of neuropeptides in jejunal enteric neurons is changed. A possible involvement of VIP and SP in persistent intestinal dysmotility and NPY in altered fluid secretion is discussed.

Involvement of vasoactive intestinal polypeptide in the parasympathetic vasodilatation of the rat masseter muscle

The parasympathetic vasodilatory fibres are known to innervate vessels in a rat masseter muscle via both cholinergic and non-cholinergic mechanisms. However, the non-cholinergic mechanisms are still unclear. Recently, vasoactive intestinal polypeptide (VIP) was convincingly shown to be involved in the parasympathetic vasodilatation in orofacial areas, such as submandibular glands and lower lip. However, very little is known about the rat masseter muscle. The present study was designed in the rat masseter muscle to assess (1) whether the parasympathetic nerve innervating vessels have VIP immunoreactivities, (2) whether intravenous administration of VIP induces the vasodilatation, and (3) effects of selective VIP receptor antagonist ([4Cl- d-Phe 6, Leu 17] VIP) in the presence or absence of atropine on the parasympathetic vasodilatation. The VIP immunoreactivities were found at two sites of the parasympathetic otic ganglion and nerve fibres located around vessels. The intravenous administration of VIP induced the vasodilatation, and [4Cl- d-Phe 6, Leu 17] VIP markedly decreased the vasodilatation evoked by VIP administration. The parasympathetic vasodilatation was not inhibited by [4Cl- d-Phe 6, Leu 17] VIP. However, treatment with [4Cl- d-Phe 6, Leu 17] VIP markedly decreased the parasympathetic vasodilatation when [4Cl- d-Phe 6, Leu 17] VIP was administered together with atropine. These results suggest that (1) VIP exists in the postganglionic parasympathetic nerve innervating the vessels in the masseter muscle, (2) the intravenous administration of VIP induces the vasodilatation in the masseter muscle, and (3) VIP may be involved in the parasympathetic vasodilatation in the masseter muscle when muscarinic cholinergic receptors are deactivated by either atropine or the suppression of the ACh release.

Rhythmic secretion of prolactin in rats: action of oxytocin coordinated by vasoactive intestinal polypeptide of suprachiasmatic nucleus origin.

Prolactin (PRL) is secreted from lactotrophs of the anterior pituitary gland of rats in a unique pattern in response to uterine cervical stimulation (CS) during mating. Surges of PRL secretion occur in response to relief from hypothalamic dopaminergic inhibition and stimulation by hypothalamic releasing neurohormones. In this study, we characterized the role of oxytocin (OT) in this system and the involvement of vasoactive intestinal polypeptide (VIP) from the suprachiasmatic nucleus (SCN) in controlling OT and PRL secretion of CS rats. The effect of OT on PRL secretion was demonstrated in cultured lactotrophs showing simultaneous enhanced secretion rate and increased intracellular Ca(2+). Neurosecretory OT cells of the hypothalamic paraventricular nucleus that express VIP receptors were identified by using immunocytochemical techniques in combination with the retrogradely transported neuronal tracer Fluoro-Gold (iv injected). OT measurements of serial blood samples obtained from ovariectomized (OVX) CS rats displayed a prominent increase at the time of the afternoon PRL peak. The injection of VIP antisense oligonucleotides into the SCN abolished the afternoon increase of OT and PRL in CS-OVX animals. These findings suggest that VIP from the SCN contributes to the regulation of OT and PRL secretion in CS rats. We propose that in CS rats the regulatory mechanism(s) for PRL secretion comprise coordinated action of neuroendocrine dopaminergic and OT cells, both governed by the daily rhythm of VIP-ergic output from the SCN. This hypothesis is illustrated with a mathematical model.

Involvement of vasoactive intestinal polypeptide in nicotine-induced relaxation of the rat gastric fundus.

1. Nicotine-induced relaxation and release of vasoactive intestinal polypeptide (VIP)- and peptide histidine isoleucine (PHI)-like immunoreactivity (LI) were measured in longitudinal muscle strips from the rat gastric fundus. 2. Under non-cholinergic conditions (0.3 microM atropine), nicotine (3-300 microM) produced concentration-dependent relaxations of the 5-hydroxytryptamine (3 microM)-precontracted strips. Under non-adrenergic non-cholinergic (NANC) conditions (0.3 microM atropine + 1 microM phentolamine + 1 microM nadolol), relaxations induced by sub-maximal nicotine concentrations (10 and 30 microM) were significantly smaller, while that produced by the highest concentration used (300 microM) was similar to that seen under non-cholinergic conditions. 3. Re-exposure to the same nicotine concentration 1 h later induced smaller relaxations, indicating desensitization. The reductions seen in the second responses were proportional to the concentration used. 4. Under non-cholinergic conditions, the relaxant response to 30 microM nicotine was abolished by hexamethonium (100 microM) and significantly reduced by tetrodotoxin (TTX, 3 microM). The TTX-resistant component was not observed under NANC conditions. 5. NANC relaxation induced by 30 microM nicotine was significantly reduced by a specific anti-VIP serum (approximately 35% less than that seen with normal rabbit serum). 6. Nicotine (30-300 microM) caused significant, concentration-dependent increases in the outflow of VIP- and PHI-LI from the strips; these effects were also diminished with re-exposure. The increases in both types of immunoreactivity evoked by nicotine (300 microM) were abolished by hexamethonium (300 microM), TTX (3 microM) and a calcium-free medium. 7. These findings indicate that VIP and possibly PHI are involved in NANC relaxation of the rat gastric fundus induced by nicotine.

Age-related changes of VIP, NPY and somatostatin-immunoreactive neurons in the cerebral cortex of aged rats

Recent studies have explored certain changes with aging of neurons containing neuropeptides. The degree of loss of vasoactive intestinal polypeptide (VIP)-, neuropeptide Y (NPY)- and somatostatin-containing neurons in the aged CNS has not yet been established with certainty however, and available data is often contradictory. Changes with aging of VIP- and NPY-containing neurons were demonstrated by immunocytochemistry in this study. A major loss of VIP-immunoreactive (ir) neurons in aged rat brain was observed in the frontal cortex area 3, parietal cortex area 1, hindlimb area, temporal cortex area 1 and 2, monocular part of occipital cortex area 1, occipital cortex area 2, and retrosplenial cortex. VIP-ir cells in the frontal cortex areas 1 and 2, parietal cortex area 2, forelimb area, binocular part of the occipital cortex area 1, and the dentate gyrus were moderately decreased. The axis of VIP neurons in the aged group showed an irregular orientation tendency, especially in layers II and III. Major loss of NPY-ir neurons in aged rat brain were observed in the retrosplenial cortex, frontal cortex areas 1 and 2, parietal cortex areas 1 and 2, occipital cortex areas 1 and 2, the temporal cortex, hippocampus proper and cingulate cortex. Loss of NPY-ir neurons was observed mostly in layers V and VI. The number and length of dendritic branches also appeared to have decreased and shortened in the aged group. There were only slight decreases of somatostatin-ir cell numbers in the parietal and occipital cortex of the aged group. These results indicate the involvement of VIP and NPY-ir neurons in the aging process of cerebral cortex, and provide the morphological evidence for the decreased number of VIP and NPY neurons by immunocytochemistry in each area of cerebral cortex of aged rats. © 1997 Elsevier Science B.V. All rights reserved.

Possible involvement of vasoactive intestinal polypeptide in the central stimulating action of pituitary adenylate cyclase-activating polypeptide on prolactin secretion in the rat

Effect of pituitary adenylate cyclase-activating polypeptide (PACAP) on prolactin (PRL) secretion was studied in Wistar strain male rats in vivo. Intravenous injection of PACAP-38 and PACAP-27 resulted in a dose-related increase in plasma PRL levels both in conscious rats and in urethane-anesthetized rats. In anesthetized animals, i.c.v. injection of PACAP-38 and PACAP-27 also elicited a dose-related increase in plasma PRL. The PRL secretion induced by i.c.v. injection of PACAP-38 was attenuated by pretreatment with rabbit antiserum to vasoactive intestinal polypeptide (VIP). These findings suggest that PACAPs stimulate PRL secretion in the rat by acting not only directly on the pituitary but also indirectly through the central nervous system, at least partly, via hypothalamic VIP.

Extrahypothalamic distribution of vasoactive intestinal polypeptide (VIP)-like immunoreactivity in the chicken brain, Gallus domesticus

The distribution of VIP-immunoreactive neurons and fibers was detected in the extrahypothalamic areas of chicken brain by immunohistochemistry and light microscopy VIP-ir perikarya were found in the hippocampus and in the area parahippocampalis; in the area ventralis of Tsai, in the n. interpeduncularis, in the substantia nigra, in the substantia grisea centralis, in the locus coeruleus, in the n. subcoeruleus ventralis and in the n. pontis lateralis. VIP-ir fibers were seen in the lobus parolfactorius and throughout the brainstem mainly arranged in lateral and midsagittal position. This finding was discussed in relation to other studies performed on chicken and/or other avian brain. The distributional pattern of VIP-ergic system in the chicken brain suggests a possible involvement of VIP or VIP-like peptide in several neuroregulatory mechanisms.

Regional Cerebral Blood Flow and Vasoactive Intestinal Polypeptide (VIP) in Rat Exposed to Whole-body Vibration Stress

To clarify the involvement of vasoactive intestinal polypeptide (VIP) in regional cerebral circulation during whole-body vibration (WBV), we determined regional cerebral blood flow and VIP-like immunoreactivity (VIP-LI) in rats following WBV for 90 min. at various accelerations (0, 2G and 4G rms), using the hydrogen gas electrolytic method. Interference electrodes were inserted into the frontal cortex and the hippocampus. Although we observed no change in hippocampal blood flow, the frontal cortical blood flow increased during the exposure in a manner that was dependent upon the acceleration. There was a significant reduction in hippocampal VIP-LI following WBV at an acceleration of 4G. The association between frontal cortical blood flow and hippocampal VIP-LI was significantly negative. Our results indicated that a local increase in blood flow in the frontal cortex of rats was induced by WBV. This increase seemed to be involved in the neural activation induced by WBV. Hippocampal VIP may have a role in the physiological regulation of frontal cortical circulation during WBV stress.

Involvement of vasoactive intestinal polypeptide in gastric reflex relaxation

We have previously presented evidence for a non-adrenergic, vagally mediated colono-gastric inhibitory reflex induced by distension of the colon. We also found that pain stimulation by putting pressure on a testicle induced a pronounced gastric relaxation mediated by both adrenergic and vagal non-adrenergic fibers in anesthetized rats. Previous in vitro studies by other workers have strongly indicated that vasoactive intestinal polypeptide (VIP) is a neural mediator of gastric relaxation. The aim of the present in vivo study was to investigate, in anesthetized rats, whether VIP is involved in the gastric reflex relaxation induced by colonic distension and pain stimulation. A volumetric method was used to monitor changes in gastric volume. Gastric reflex relaxation following colonic distension was significantly and markedly inhibited by VIP antiserum as compared to the control relaxation before administration of the antiserum. Non-immunized control serum did not significantly influence gastric relaxation caused by colonic distension. Pain-induced gastric relaxation was moderately but significantly reduced after the administration of VIP antiserum but not after control serum. The selective β 2-adrenoceptor agonist, salbutamol, induced a pronounced gastric relaxation of the same magnitude before and after the administration of VIPantiserum. VIP antiserum changed the pattern of gastric motility by inducing a specific type of gastric contraction appearing spontaneously or in response to colonic distension. A close intra-arterial injection of VIP induced gastric relaxation and inhibition of phasic gastric contractions. The present results in the rat suggest that VIP or a VIP-like peptide is involved in gastric reflex relaxation induced by colonic distension and pain stimulation.

Vasoactive Intestinal Polypeptide/Peptide Histidine Isoleucine-Immunoreactive Neuron Systems in the Basal Hypothalamus of a Rat Strain with Deficient Prolactin Release in Response to Stress

There is evidence for involvement of vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine (PHI) in control of prolactin secretion. In fact VIP- and PHI-like immunoreactivities have been demonstrated in the hypotha/amic paraventricular nucleus and at the median eminence level. Using immunohistochemistry we have compared the distribution of immunoreactive VIP and PHI in the hypothalamus of male Sprague-Dawley rats and BS rats, a rat strain which has a deficient release of prolactin after stressful stimuli. Quantitative information was obtained by radioimmunoassay for VIP. VIP- and PHI-positive cell bodies were found in the parvocellular part of the paraventricular nucleus in colchicine-treated rats and in nerve fibres within the median eminence of untreated rats to the same extent in both strains. Furthermore, intravenous injection of VIP caused a significant increase in serum prolactin tevets in both strains. However, at the median eminence level in BS rats, the blood vessels located in the lateral aspects of the median eminence did not show the dense VIP/PHI innervation seen in Sprague-Dawley rats. Also, a thick VIP/PHI-positive nerve bundle present on the surface of the median eminence of Sprague-Dawley rats could not be seen in BS rats. Radioimmunoassay analysis revealed that VIP levels in the median eminence were twice as high in Sprague-Dawley as compared to BS rats. Taken together, these results suggest that the defect in the prolactin release mechanism present in BS rats is not confined to the paraventricular system or the pituitary, but could be due to a deficit in VIP/PHI in fibres associated with portal vessels at the median eminence level.

Vasoactive intestinal polypeptide nerve fibers in human and monkey ( Macaca fascicularis and Macaca mulatta) kidneys

Nerve fibers immunoreactive for vasoactive intestinal polypeptide (VIP) were demonstrated for the first time by the indirect immunofluorescence technique in human and monkey kidneys. VIP-immunoreactive nerve fibers showing varicosities were observed in the adventitia of arcuate arteries and their branches. The density of VIP-immunoreactive nerve fibers decreased from the juxtamedullary region to the cortex. Occasionally a VIP-immunoreactive varicose nerve fiber was observed near the vascular pole of a glomerulus, but no direct innervation of afferent or efferent arterioles in either monkey or human kidney was found. The distribution of VIP-immunoreactive nerve fibers in the monkey and human kidneys was similar to that reported in other species, with less density. The functional role of VIP in the innervation of the kidney is not known, but various suggestions have been made regarding the possible involvement of VIP on vasodilation of selective intrarenal blood vessels, renin secretion, and/or effects on tubules. While none of these questions were established at this time they would appear to be logical areas for further study.

Intraventricular injection of vasoactive intestinal polypeptide facilitates the development of amygdaloid kindling

To determine the involvement of vasoactive intestinal polypeptide (VIP) in the development of kindling in rats, VIP or antibody to VIP (anti-VIP) was injected into the third ventricle after the daily stimulation of the basolateral amygdala. The number of stimulations required to reach full amygdaloid kindling was significantly smaller in rats treated with VIP than rats treated with saline, whereas it increased significantly in rats treated with anti-VIP compared to that in the rats treated with either saline or normal rabbit serum. The results suggest that VIP participates in the development of amygdaloid kindling as a facilitatory factor.

Direct evidence for the involvement of vasoactive intestinal polypeptide in the motor response of the human isolated ileum to capsaicin

Capsaicin (1 μM) produced complex motor responses in longitudinal and circular muscle strips from the human isolated small intestine (jejunum and ileum). In the longitudinal muscle, inhibition of the nerve-mediated contractions (electrical field stimulation) was the dominant response, while capsaicin had a weak and inconsistent effect on tone and spontaneous activity. In contrast, relaxation and decreased spontaneous activity were the responses of the circular muscle to capsaicin. These effects of capsaicin were not reproduced by a second application of capsaicin, indicating desensitization, a feature of the specific action of this drug on sensory nerves. All the effects of capsaicin in the longitudinal and circular muscle were closely mimicked by exogenous vasoactive intestinal polypeptide (VIP). Further, the inhibitory motor effect of capsaicin in both muscle layers was blocked by an anti VIP serum. In the longitudinal muscle, VIP, like capsaicin, inhibited the electrically evoked nerve-mediated contractions but not the tetrodotoxin-resistant myogenic contractions, suggesting a prejunctional site of action. The inhibitory effect of both capsaicin and VIP in the circular muscle was tetrodotoxin-resistant suggesting direct inhibition of muscle cells. Capsaicin (1 μM) evoked a tetrodotoxin-resistant release of VIP-like immunoreactivity from the human small intestine. On high pressure liquid chromatography, a major peak of the immunoreactive material released by capsaicin co-eluted with authentic VIP and a minor, unidentified peak eluted shortly afterward. We conclude that authentic VIP is involved in the local motor response to capsaicin in the human small intestine. These findings raise the possibility that VIP might be present in sensory nerves of the human gut from which it is released by capsaicin.

Comparison of the effect of vasoactive intestinal polypeptide and non-adrenergic non-cholinergic neurone stimulation in the cat gastric fundus

The possible involvement of vasoactive intestinal polypeptide (VIP) in the non-adrenergic non-cholinergic (NANC) relaxation of the cat gastric fundus was studied in circular and longitudinal muscle strips. Cumulative transmural stimulation induced a frequency-dependent relaxation, while cumulative administration of VIP induced a concentration-dependent relaxation. Tetrodotoxin almost completely antagonized the relaxation induced by transmural stimulation (1 Hz), but did not influence the relaxation induced by VIP (10 −7 M); the latter was not influenced by hexamethonium or propranolol plus phentolamine. Trypsin (30 min incubation) and VIP antiserum (1 h incubation) prevented the relaxation induced by VIP and reduced that induced by transmural stimulation, but did not influence the relaxation induced by isopropylnoradrenaline. Two putative VIP receptor antagonists, [AcTyr 1]hGRF-(1–40)OH and [4Cl-D-Phe 6,Leu 17]VIP, did not influence the relaxation induced by VIP or transmural stimulation. These results are compatible with the hypothesis that VIP is involved in the NANC relaxation of the cat gastric fundus, although participation of a non-VIP component cannot be excluded.