vasoactive-intestinal-peptide and Enteritis

The cellular mechanisms of motility dysfunction in postinfectious irritable bowel syndrome (PI-IBS) are not known. We used a rat model of neonatal inflammation to test the hypothesis that gene plasticity in colonic circular smooth muscle cells underlies motility dysfunction in PI-IBS. Mild/moderate or severe inflammation was induced in neonatal and adult rats. Experiments were performed in tissues obtained at 7 days (short term) and 6-8 wk (long term) after the induction of inflammation. Severe inflammation in neonatal rats induced persistent long-term smooth muscle hyperreactivity to acetylcholine (ACh), whereas that in adult rat caused smooth muscle hyporeactivity that showed partial recovery in the long term. Mild/moderate inflammation had no effect in neonatal rats, but it induced smooth muscle hyporeactivity to ACh in adult rats, which recovered fully in the long term. Smooth muscle hyperreactivity to ACh resulted in accelerated colonic transit and increase in defecation rate, whereas hyporeactivity had opposite effects. Smooth muscle hyperreactivity to ACh was associated with increase in transcription rate of key cell-signaling proteins of the excitation-contraction coupling alpha1C subunit of Cav1.2 (L-type) calcium channels, Galphaq, and 20-kDa myosin light chain (MLC20), whereas hyporeactivity was associated with their suppression. Inflammation in adult rats induced classical inflammatory response, which was absent in neonatal rats. Severe neonatal inflammation enhanced plasma norepinephrine and muscularis propria vasoactive intestinal polypeptide in the long term. We conclude that severe, but not mild/moderate, inflammation in a state of immature or impaired stress and immune response systems alters the transcription rate of key cell-signaling proteins of excitation-contraction coupling in colonic circular smooth muscle cells to enhance their contractility and accelerate colonic transit and defecation rate.

Topics: Acetylcholine; Age Factors; Animals; Animals, Newborn; Calcium Channels, L-Type; Cholinergic Agents; Colon; Defecation; Disease Models, Animal; Enteric Nervous System; Enteritis; Gastrointestinal Motility; Gene Expression Regulation; GTP-Binding Protein alpha Subunits, Gq-G11; Inflammation Mediators; Irritable Bowel Syndrome; Male; Myocytes, Smooth Muscle; Myosin Light Chains; Rats; Rats, Sprague-Dawley; Severity of Illness Index; Signal Transduction; Vasoactive Intestinal Peptide

We investigated the effects of an enteric infection with the parasitic nematode, Trichinella spiralis, on peptidergic and cholinergic neural pathways of the guinea pig jejunum. The content of the enteric neuropeptides, substance P (SP) and vasoactive intestinal peptide (VIP), and the activities of the key cholinergic enzymes, acetylcholinesterase (AChE) and choline acetyltransferase (ChAT), were measured and compared in extracts of jejunal muscularis externa (ME) obtained from uninfected jejunum and T. spiralis-inflamed jejunum. Significant decreases were detected in both SP immunoreactivity and AChE activity on days 6 and 10 postinfection (PI) in nematode-infected guinea pig jejunum compared to uninfected controls. The maximum changes observed for SP and AChE both occurred on day 10 PI and were evident as decreases of 37% and 48%, respectively, from the mean uninfected control values for SP and AChE. In contrast, VIP immunoreactivity and ChAT activity showed no significant changes during the enteric phase of T. spiralis infection. Nematode-evoked histopathological changes in jejunal tissues from infected animals were associated with significant increases in myeloperoxidase (MPO) activity, an index of inflammation intensity, which occurred on day 6 PI (885% of mean control) and day 10 PI (469% of mean control) coinciding temporally with the significant decrease in SP content and AChE activity during infection. Thus, intestinal motor disturbances observed in mammalian hosts during enteric nematode infections involve inflammation-generated changes in the neurohumoral control of smooth muscle function.

Topics: Acetylcholinesterase; Animals; Choline O-Acetyltransferase; Enteritis; Guinea Pigs; Intestinal Diseases, Parasitic; Jejunal Diseases; Jejunum; Male; Neuropeptides; Peroxidase; Substance P; Trichinella spiralis; Trichinellosis; Vasoactive Intestinal Peptide

Reports suggest that vasoactive intestinal peptide (VIP) binds to lymphocytes and modulates immune responses. The intestines are richly innervated with VIP-producing nerves. Thus, VIP from nerves or other sources may participate in mucosal immunoregulation. To explore this hypothesis further, murine intestinal mucosal inflammatory cells were scrutinized for functional VIP receptors. An [125I]VIP competitive binding assay characterized VIP receptors. Unfractionated lamina propria inflammatory cells bound [125I]VIP specifically. This binding was abrogated by T cell depletion. The VIP receptor on lamina propria T cells was of a single class with a Kd of 9.08 x 10(-9) M. It bound PHI and other peptide analogs poorly. The intestinal epithelial cell had a high-affinity VIP receptor (Kd 4.17 x 10(-10) M) that bound one VIP analog with moderate affinity. Both VIP and ConA stimulated mucosal inflammatory cells to release interleukin-5 (IL-5). Mucosal inflammatory cells depleted of T cells did not release IL-5 in response to VIP or ConA. It is concluded that: (1) some murine mucosal T lymphocytes have VIP receptors that may be distinct from those displayed on mucosal epithelial cells; (2) VIP affects mucosal T lymphocyte function.

Topics: Animals; Enteritis; Interleukin-5; Intestinal Mucosa; Mice; Mice, Inbred CBA; Receptors, Gastrointestinal Hormone; Receptors, Vasoactive Intestinal Peptide; T-Lymphocytes; Vasoactive Intestinal Peptide