Increase In Vasoactive Intestinal Peptide Research Articles

Experimental Cancer Cachexia Changes Neuron Numbers and Peptide Levels in the Intestine: Partial Protective Effects after Dietary Supplementation with L-Glutamine

Gastrointestinal dysmotility frequently occurs in cancer cachexia and may result from damage to enteric innervation caused by oxidative stress, especially due to glutathione depletion. We assessed the effect of dietary supplementation with 20 g/kg l-glutamine (a glutathione precursor) on the intrinsic innervation of the enteric nervous system in healthy and Walker 256 tumor-bearing Wistar rats during the development of experimental cachexia (14 days), in comparison with non-supplemented rats, by using immunohistochemical methods and Western blotting. The total neural population and cholinergic subpopulation densities in the myenteric plexus, as well as the total population and VIPergic subpopulation in the submucosal plexus of the jejunum and ileum, were reduced in cachectic rats, resulting in adaptive morphometric alterations and an increase in vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP) expression, suggesting a neuroplastic response. l-glutamine supplementation prevented decrease in myenteric neuronal density in the ileum, morphometric alterations in the neurons and nerve fibers (in both the plexuses of the jejunum and ileum), and the overexpression of VIP and CGRP. Cancer cachexia severely affected the intrinsic innervation of the jejunum and ileum to various degrees and this injury seems to be associated with adaptive neural plasticity. l-glutamine supplementation presented partial protective effects on the enteric innervation against cancer cachexia, possibly by attenuating oxidative stress.

Unbalanced Peptidergic Inhibition in Superficial Neocortex Underlies Spike and Wave Seizure Activity.

Slow spike and wave discharges (0.5-4 Hz) are a feature of many epilepsies. They are linked to pathology of the thalamocortical axis and a thalamic mechanism has been elegantly described. Here we present evidence for a separate generator in local circuits of associational areas of neocortex manifest from a background, sleep-associated delta rhythm in rat. Loss of tonic neuromodulatory excitation, mediated by nicotinic acetylcholine or serotonin (5HT3A) receptors, of 5HT3-immunopositive interneurons caused an increase in amplitude and slowing of the delta rhythm until each period became the "wave" component of the spike and wave discharge. As with the normal delta rhythm, the wave of a spike and wave discharge originated in cortical layer 5. In contrast, the "spike" component of the spike and wave discharge originated from a relative failure of fast inhibition in layers 2/3-switching pyramidal cell action potential outputs from single, sparse spiking during delta rhythms to brief, intense burst spiking, phase-locked to the field spike. The mechanisms underlying this loss of superficial layer fast inhibition, and a concomitant increase in slow inhibition, appeared to be precipitated by a loss of neuropeptide Y (NPY)-mediated local circuit inhibition and a subsequent increase in vasoactive intestinal peptide (VIP)-mediated disinhibition. Blockade of NPY Y1 receptors was sufficient to generate spike and wave discharges, whereas blockade of VIP receptors almost completely abolished this form of epileptiform activity. These data suggest that aberrant, activity-dependent neuropeptide corelease can have catastrophic effects on neocortical dynamics.

Chlorine inhalation produces nasal airflow limitation in allergic rhinitic subjects without evidence of neuropeptide release

Seasonal allergic rhinitic (SAR) subjects are more physiologically reactive to airborne irritants than non-rhinitic (NR) subjects; however the mechanism underlying this difference is unclear. We sought to determine whether irritant-induced nasal airflow limitation involves neuropeptide release into nasal lining fluid, and if so, whether such release occurs differentially by rhinitic status. Eight SAR and 8 NR subjects were exposed to 1.0 ppm chlorine and filtered air in random order during separate visits; exposures were via nasal mask and lasted 15 min. Rhinomanometry was performed before, immediately post-, and 15 min post-exposure. Following a minimum of 2 weeks' time, exposures and symptom reporting were repeated with nasal lavage pre- and post-exposure. Neuropeptides (substance P, cacitonin gene-related protein, vasoactive intestinal peptide, and neuropeptide Y) as well as markers of plasma leakage (albumin and urea) and glandular secretion (lysozyme and 7F10-mucin) were measured using standard methods. Cl(2) provocation significantly increased nasal airway resistance in SAR but not NR subjects (p<0.05). Neuropeptide levels in nasal lavage fluid, on the other hand, were unaffected, with the exception of a paradoxical increase in vasoactive intestinal peptide in non-rhinitic controls post-Cl(2) provocation. Irritant-induced nasal airflow limitation is more pronounced among SAR than NR subjects. We could not, however, demonstrate a role for neuropeptide release in the nasal congestive response of SAR subjects.

5-HT4 receptor agonists and delta-opioid receptor antagonists act synergistically to stimulate colonic propulsion.

Opioid neurons exert a tonic restraint on inhibitory VIP/PACAP/NOS motoneurons of the enteric nervous system. A decrease in opioid peptide release during the descending phase of the peristaltic reflex, which underlies propulsive activity, leads to an increase in vasoactive intestinal peptide (VIP), pituitary adenylate cyclase-activating polypeptide (PACAP), and nitric oxide (NO) release and circular muscle relaxation. These effects are accentuated by opioid receptor antagonists. Endogenous opioid peptides and selective opioid delta-, kappa- and mu-receptor agonists decreased the velocity of pellet propulsion in isolated segments of guinea pig colon, whereas selective antagonists increased velocity in a concentration-dependent fashion with an order of potency indicating preferential involvement of delta-receptors. 5-HT4 agonists (HTF-919 and R-093877), which also increase the velocity of propulsion, acted synergistically with the delta-receptor antagonist naltrindole; a threshold concentration of naltrindole (10 nM) shifted the concentration-response curve to HTF-919 to the left by 70-fold. A combination of 10 nM naltrindole with threshold concentrations of the 5-HT4 agonists caused significant increases in the velocity of propulsion (50 +/- 7 to 77 +/- 8%). We conclude that 5-HT4 agonists and opioid delta-receptor antagonists act synergistically to facilitate propulsive activity in isolated colonic segments.

Early increase of vasoactive intestinal peptide in acute myocardial infarction

Early increase of vasoactive intestinal peptide in acute myocardial infarction

Substance P, calcitonin gene-related peptide, and vasoactive intestinal peptide increase in nasal secretions after allergen challenge in atopic patients

Background: There is suggestive evidence that neuropeptides participate in allergic reactions. Substance P (SP) and calcitonin gene-related peptide (CGRP) are released by sensory nerves, whereas vasoactive intestinal peptide (VIP) is released mainly by parasympathetic nerves. Both sets of nerves are thought to be stimulated by allergic inflammation. The aim of this study was to assess nasal secretions to determine whether SP, CGRP, and VIP were increased after allergen challenge. Methods: Eight patients with allergic rhinitis were challenged nasally with 1 mg histamine or increasing doses of allergen. Nasal lavages were collected into a cocktail of protease inhibitors in order to restrict neuropeptide degradation. Radioimmunoassay for SP, CGRP, and VIP were performed on each sample. Results: All patients had immediate clinical reactions to both histamine and allergen challenges, and seven patients experienced a later allergic reaction. After histamine challenge, SP and CGRP did not increase significantly above baseline in the nasal lavages, whereas VIP did ( p < 0.02). In contrast, SP, CGRP, and VIP all significantly increased immediately after allergen challenge and returned to baseline within 2 hours. At the clinical peak of the late allergic reaction, SP, but not CGRP or VIP, was increased slightly but significantly ( p < 0.01). Conclusions: Thus SP, CGRP, and VIP are found in nasal secretions after allergen challenge, which confirms that neuropeptides are released in human beings during allergic reactions. The selective stimulation of VIP secretion by histamine challenge suggests that histamine-induced cholinergic reflexes induce the release of VIP. These data support the suggestion that neuropeptides may be partly responsible for some of the nasal symptoms of allergy.

Gastrin secretion induced by distention is mediated by gastric cholinergic and vasoactive intestinal peptide neurons in rats

Background: The present study was designed to identify the mechanism by which distention regulates gastrin secretion. Methods: The distal stomach of the isolated vascularly perfused rat was distended to varying degrees for 10-minute periods with an air-filled balloon. Results: Low distention caused a decrease in gastrin (39% ± 5%; P < 0.001) and an increase in somatostatin (58% ± 4%; P < 0.001) secretion. High distention caused an opposite effect, i.e., an increase in gastrin (49% ± 11%; P < 0.01) and a decrease in somatostatin (44% ± 11%; P < 0.01) secretion. All responses were abolished by the axonal blocker, tetrodotoxin. Atropine had no effect on the responses to low distention, but converted the pattern of response with high distention to that observed with low distention. Both high and low distention were accompanied by a sustained increase in vasoactive intestinal peptide (VIP) secretion. The selective VIP antagonist, VIP[10–28], abolished both the gastrin and somatostatin responses to low distention. Conclusions: Low gastric distention activates preferentially VIP neurons that stimulate somatostatin and thus inhibit gastrin secretion. Increasing distention leads to progressive recruitment of cholinergic neurons that cause a reversal in the pattern to one of increase in gastrin and decrease in somatostatin secretion.

Pituitary adenylate cyclase activating polypeptide and vasoactive intestinal peptide increase cytosolic free calcium concentration in cultured rat hippocampal neurons

Pituitary adenylate cyclase activating polypeptide and vasoactive intestinal peptide increase cytosolic free calcium concentration in cultured rat hippocampal neurons

Distinct regulation of vasoactive intestinal peptide (VIP) expression at mRNA and peptide levels in human neuroblastoma cells

Neuronal differentiation was induced in cultures of the human neuroblastoma cell line subclone SH-SY5Y by 14-day treatment with dibutyryl cAMP (dBcAMP), retinoic acid, and phorbol 12-myristate 13-acetate (PMA). An approximate 4-fold increase in vasoactive intestinal peptide (VIP) mRNA concentration was observed after differentiation with retinoic acid, whereas no change in VIP mRNA concentration was observed after differentiation with dBcAMP or PMA. A short-term treatment of cells with PMA did however result in a 5-fold transient increase in VIP mRNA; prior differentiation with retinoic acid or dBcAMP diminished this effect. Observed increases in VIP mRNA were in all cases accompanied by increases in VIP immunoreactivity. Remarkably, however, long-term treatment of cells with dBcAMP, which caused no change in mRNA levels, resulted in a six-fold increase in VIP immunoreactivity. Acute (36-h) treatment with carbachol also caused an increase in VIP immunoreactivity (about 2-fold, and blocked by atropine) without an increase in VIP mRNA level. Thus, a quantitative change in gene transcription or mRNA stability appears not to be a prerequisite for increased VIP expression, indicating that regulation can occur at translational or post-translational steps.

Effect of Massive Small Bowel Resection on Components of the Peptidergic Innervation of the Rat Small Intestine

The effect of massive small bowel resection on the immunostaining of neuropeptides in the submucous plexus of the retained small intestine was examined. The neuropeptides chosen were somatostatin and vasoactive intestinal polypeptide because these are markers for two of the major populations of neurons in the plexus. Three different methods were used to assess the effect of resection on the enteric nervous system. Firstly immunocytochemical staining of neuropeptide containing neurons and nerve fibers was compared between test and control animals. The results demonstrated a significant increase in the number and size of the vasoactive intestinal polypeptide containing neurons with no change in the number of somatostatin neurons although these were also increased in size. Secondly the possibility that the increase in neuron number might be the result of neuronal division was examined by 3H-thymidine incorporation experiments. The results demonstrated that no neuronal elements were labelled. Finally the possibility that the increase in vasoactive intestinal peptide was the result of an increase in transcription was assessed by Northern blot analysis. The results demonstrated a small but significant increase in mRNA levels. It was concluded that massive small bowel resection directly affects neuropeptide levels in the submucous plexus, resulting in an increase in vasoactive intestinal polypeptide-immunoreactive neurons.

Opiate modulation of the stress-induced increase of vasoactive intestinal peptide (VIP) in plasma.

Vasoactive intestinal peptide (VIP) has a variety of extra-intestinal actions which are typical of the body's reaction to stress, such as lipolysis, glycogenolysis and modulation of anterior pituitary hormone secretion. Serial VIP plasma concentrations in patients undergoing major laparotomies were determined. The influence of the mu-receptor agonist, fentanyl, on intra-operative changes was investigated and compared to a control group receiving halothane anesthesia. Plasma levels of typical "stress hormones" cortisol and catecholamines were also monitored for additional information on the extent of perioperative stress. VIP levels increased intraoperatively in the halothane group from 5.9 +/- 4.6 to 15.3 +/- 5.3 pmol/l. Cortisol and catecholamine levels showed a similar increase. The intraoperative VIP increase in the fentanyl group was significantly smaller: 3.5 +/- 1.9 to 7.3 +/- 3.6 pmol/l. Anesthesia itself did not affect VIP concentrations as shown by constant levels during a 30 minute preoperative control period. The observed increases of VIP plasma concentration are thought to reflect a possible role for VIP in the hormonal metabolic response to stress. The attenuation of the increase by fentanyl might be due to a direct opiate action on VIP release.

Accumulation of biological amines into chromaffin granules: a model for hormone and neurotransmitter transport.

Accumulation of biological amines into chromaffin granules: a model for hormone and neurotransmitter transport.