122 research outputs found
Alteration of nitrergic neuromuscular transmission as a result of acute experimental colitis in rat
Nitric oxide (NO) is a non-adrenergic, non-cholinergic neurotransmitter found in the enteric nervous system that plays a role in a variety of enteropathies, including inflammatory bowel disease. Alteration of nitrergic neurons has been reported to be dependent on the manner by which inflammation is caused. However, this observed alteration has not been reported with acetic acid-induced colitis. Therefore, the purpose of the current study was to investigate changes in nitrergic neuromuscular transmission in experimental colitis in a rat model. Distal colitis was induced by intracolonic administration of 4% acetic acid in the rat. Animals were sacrificed at 4 h and 48 h post-acetic acid treatment. Myeloperoxidase activity was significantly increased in the acetic acid-treated groups. However, the response to 60 mM KCl was not significantly different in the three groups studied. The amplitude of phasic contractions was increased by Nω-nitro-L-arginine methyl ester (L-NAME) in the normal control group, but not in the acetic acid-treated groups. Spontaneous contractions disappeared during electrical field stimulation (EFS) in normal group. However, for the colitis groups, these contractions initially disappeared, and then reappeared during EFS. Moreover, the observed disappearance was diminished by L-NAME; this suggests that these responses were NO-mediated. In addition, the number of NADPH-diaphorase positive nerve cell bodies, in the myenteric plexus, was not altered in the distal colon; whereas the area of NADPH-diaphorase positive fibers, in the circular muscle layer, was decreased in the acetic acid-treated groups. These results suggest that NO-mediated inhibitory neural input, to the circular muscle, was decreased in the acetic acid-treated groups
The Expression of Vasoactive Intestinal Peptide Receptor 1 Is Negatively Modulated by MicroRNA 525-5p
Background: The human Vasoactive Intestinal Peptide (VIP) is a neurokine with effects on the immune system where it is involved in promoting tolerance. In this context, one of its receptors, VPAC1, has been found to be down-modulated in cells of the immune network in response to activating stimuli. In particular, the bacterial liposaccaride (LPS), a strong activator of the innate immune system, induces a rapid decrease of VPAC1 expression in monocytes and this event correlates with polymorphisms in the 3'-UTR of the gene. Methodology/Principal Findings: MicroRNA 525-5p, having as putative target the 3'-UTR region of VPAC1, has been analysed for its expression in monocytes and for its role in down-modulating VPAC1 expression. We report here that miR-525-5p is promptly up-regulated in LPS-treated monocytes. This microRNA, when co-transfected in 293T cells together with a construct containing the 3'-UTR of the VPAC1 gene, significantly reduced the luciferase activity in a standard expression assay. The U937 cell line as well as primary monocytes enforced to express miR-525-5p, both down-modulate VPAC1 expression at similar extent. Conclusions/Significance: Our results show that the response to an inflammatory stimulus elicits in monocytes a rapid increase of miR-525-5p that targets a signaling pathway involved in the control of the immune homeostasis
Somatostatin, substance P and calcitonin gene-related peptide-positive intramural nerve structures of the human large intestine affected by carcinoma.
Protective Intestinal Effects of Pituitary Adenylate Cyclase Activating Polypeptide
Pituitary adenylate cyclase activating polypeptide (PACAP) is an
endogenous neuropeptide widely distributed throughout the body, including the
gastrointestinal tract. Several effects have been described in human and animal
intestines. Among others, PACAP infl uences secretion of intestinal glands, blood
fl ow, and smooth muscle contraction. PACAP is a well-known cytoprotective peptide
with strong anti-apoptotic, anti-infl ammatory, and antioxidant effects. The
present review gives an overview of the intestinal protective actions of this neuropeptide.
Exogenous PACAP treatment was protective in a rat model of small bowel
autotransplantation. Radioimmunoassay (RIA) analysis of the intestinal tissue showed that endogenous PACAP levels gradually decreased with longer-lasting
ischemic periods, prevented by PACAP addition. PACAP counteracted deleterious
effects of ischemia on oxidative stress markers and cytokines. Another series of
experiments investigated the role of endogenous PACAP in intestines in PACAP
knockout (KO) mice. Warm ischemia–reperfusion injury and cold preservation models
showed that the lack of PACAP caused a higher vulnerability against ischemic
periods. Changes were more severe in PACAP KO mice at all examined time points.
This fi nding was supported by increased levels of oxidative stress markers and
decreased expression of antioxidant molecules. PACAP was proven to be protective
not only in ischemic but also in infl ammatory bowel diseases. A recent study showed
that PACAP treatment prolonged survival of Toxoplasma gondii infected mice suffering
from acute ileitis and was able to reduce the ileal expression of proinfl ammatory
cytokines. We completed the present review with recent clinical results obtained
in patients suffering from infl ammatory bowel diseases. It was found that PACAP
levels were altered depending on the activity, type of the disease, and antibiotic
therapy, suggesting its probable role in infl ammatory events of the intestine
Changes in vasoactive intestinal peptide, pituitary adenylate cyclase-activating polypeptide and neuropeptide Y-ergic structures of the enteric nervous system in the carcinoma of the human large intestine.
Abdominal surgery inhibits fos expression in the gastric myenteric plexus induced by intracisternal injection of TRH analog, RX-77368 in consclous rats
Peripheral corticotropin-releasing factor (CRF) stimulates fos expression in the rat colonic myenteric neurons andfecal pellet output through CRF receptor subtype 1
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