vasoactive-intestinal-peptide and Ulcer

The protective effect of capsaicin-sensitive sensory nerve (CSSN) activation was recently demonstrated in human gastric mucosa. We here examined changes in neuropeptides, specifically Substance P (SP), calcitonin-gene related peptide (CGRP) and vasoactive intestinal peptide (VIP) in patients with chronic gastritis or ulcer. Furthermore changes in neprilysin levels, which hydrolyse these neuropeptides, were determined. Gastric biopsies were obtained from both lesion- and normal-appearing mucosa of 57 patients. The presence of H. pylori infection was verified with rapid urease assay. Neuronal and non-neuronal levels of SP, VIP, CGRP and neprilysin activity were determined in freshly frozen biopsies. Immunohistochemical localization of neprilysin was performed in 30 paraffin embedded specimens. We here found that neuronal SP levels decreased significantly in normally appearing mucosa of patients with gastritis while levels of non-neuronal SP increased in diseased areas of gastritis and ulcer. The presence of H. pylori led to further decreases of SP levels. The content of VIP in both disease-involved and uninvolved mucosa, and expression of neprilysin, markedly decreased in patients with gastritis or ulcer. Since VIP, as well as SP fragments, formed following hydrolysis with neprilysin is recognized to have gastroprotective effects, decreased levels of VIP, SP and neprilysin may predispose to cellular damage.

Topics: Adult; Calcitonin Gene-Related Peptide; Duodenal Ulcer; Female; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Neprilysin; Neurons; Peptic Ulcer; Substance P; Ulcer; Vasoactive Intestinal Peptide; Young Adult

Impairment of small intestinal absorption has been described in patients with ulcerative colitis and in animal models of experimental colitis. The pathophysiology of this dysfunction has not been elucidated. The aim of this study was to investigate the effect of chemical colitis on jejunal fluid absorption and determine the role of the enteric nervous system and some putative neurotransmitters. In a rat model of iodoacetamide-induced colitis, jejunal net fluid absorption was evaluated by the in vivo single-pass perfusion technique. The effects of 1) tetrodotoxin (TTX), 2) benzylalkonium chloride (BAC), 3) capsaicin, 4) vasoactive intestinal polypeptide (VIP) antagonism, 5) nitric oxide (NO) synthase (NOS) inhibition, and 6) 5-hydroxytryptamine type 3 and 4 (5-HT(3) and 5-HT(4)) receptor antagonism on the changes in fluid movement were investigated. A significant decrease in jejunal net fluid absorption was found 2 and 4 days after colitis induction: 26 (SD 14) and 28 (SD 19) microl x min(-1) x g dry intestinal wt(-1), respectively [P < 0.0002 compared with sham rats at 61 (SD 6.5) microl x min(-1) x g dry intestinal wt(-1)]. No histological changes were evident in jejunal sections. TTX and BAC reversed this decrease in fluid absorption: 54 (SD 13) and 44 (SD 14) microl x min(-1) x g dry intestinal wt(-1) (P = 0.0005 and P = 0.019, respectively, compared with colitis). Ablation of capsaicin-sensitive primary afferent fibers had a partial effect: 45 (SD 5) microl x min(-1) x g dry intestinal wt(-1) (P = 0.001 and P = 0.003 compared with colitis and sham, respectively). Constitutive and neuronal NOS inhibition and VIP antagonism returned jejunal net fluid absorption to normal values: 66 (SD 19), 61 (SD 5), and 56 (SD 14) microl x min(-1) x g dry intestinal wt(-1), respectively. 5-HT(3) and 5-HT(4) receptor antagonism had no effect. Chemical colitis is associated with a significant decrease in jejunal net fluid absorption. This decrease is neurally mediated and involves VIP- and NO-related mechanisms.

Topics: Animals; Benzalkonium Compounds; Capsaicin; Colitis; Enteric Nervous System; Enzyme Inhibitors; Intestinal Absorption; Iodoacetamide; Jejunum; Male; Myenteric Plexus; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Perfusion; Rats; Rats, Sprague-Dawley; Serotonin; Serotonin Antagonists; Sulfhydryl Reagents; Tetrodotoxin; Ulcer; Vasoactive Intestinal Peptide

Rectal biopsy specimens from patients with ulcerative proctitis/proctosigmoiditis (UP/PS) were investigated immunocytochemically. In general, a changed mucosal innervation was demonstrated, with a marked increase in the number of nerve fibres and terminals with neuropeptide Y and tyrosine hydroxylase. In a few patients a hyperinnervation with VIPergic or SPergic nerves was seen. These findings indicate that hyperactive local nervous reflexes are of pathogenetic importance. To silence such activity, the diseased mucosa was treated with topically applied lidocaine. Such topical treatment with lidocaine gel in 21 consecutive patients with UP/PS for 3-8 weeks caused a rapid decrease of subjective and objective symptoms. During treatment mucosal integrity was restored, accompanied by depletion of OKT4 and OKT8 lymphocytes from the mucosa. However, the hyperinnervation pattern persisted during treatment.

Topics: Administration, Topical; Adult; Female; Humans; Immunohistochemistry; Intestinal Mucosa; Lidocaine; Male; Middle Aged; Nerve Fibers; Neuropeptide Y; Proctitis; Ulcer; Vasoactive Intestinal Peptide