TNF-α inhibits SCF, ghrelin, and substance P expressions through the NF-κB pathway activation in interstitial cells of Cajal

Ulcerative colitis is a chronic inflammatory disease of the colon where intestinal motility is disturbed. Interstitial cells of Cajal (ICC) are required to maintain normal intestinal motility. In the present study, we assessed the effect of tumor necrosis factor-alpha (TNF-α) on viability and apoptosis of ICC, as well as on the expression of stem cell factor (SCF), ghrelin, and substance P. ICC were derived from the small intestines of Swiss albino mice. Cell viability and apoptosis were measured using CCK-8 assay and flow cytometry, respectively. ELISA was used to measure the concentrations of IL-1β, IL-6, ghrelin, substance P, and endothelin-1. Quantitative RT-PCR was used to measure the expression of SCF. Western blotting was used to measure the expression of apoptosis-related proteins, interleukins, SCF, and NF-κB signaling pathway proteins. TNF-α induced inflammatory injury in ICC by decreasing cell viability and increasing apoptosis and levels of IL-1β and IL-6. TNF-α decreased the levels of SCF, ghrelin, and substance P, but had no effect on endothelin-1. TNF-α down-regulated expressions of SCF, ghrelin, and substance P by activating the NF-κB pathway in ICC. In conclusion, TNF-α down-regulated the expressions of SCF, ghrelin, and substance P via the activation of the NF-κB pathway in ICC.

Does dexamethasone act in neuropeptides SP and CGRP in neurogenic inflammation of the skin? An experimental study

PURPOSE: To investigate the neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) after subcutaneous injection of dexamethasone prior to skin incision in rats.METHODS:Twenty seven Wistar-EPM-1 rats were randomly divided into three groups. The sham group (SG) of rats was injected with 0.9 % saline. The second group (Dexa) was injected with 1.0 mg/kg dexamethasone, and the third group (Dexa+) was injected with 10.0 mg/kg dexamethasone. In all groups, the three subcutaneous injections were performed 30 minutes prior to the surgical skin incision and tissue collection. SP and CGRP (15 kDa pro-CGRP and 5 kDa CGRP) were quantified by Western Blotting.RESULTS: No statistically significant differences (p>0.05) were found in pro-CGRP, CGRP and SP values in all three groups.CONCLUSION:The anti-inflammatory effect of dexamethasone did not occur when the substance P and calcitonin gene-related peptide levels were altered during the neurogenic inflammation process of skin wound healing in rats.

Effects of DA-9701, a Novel Prokinetic Agent, on Phosphorylated Extracellular Signal-Regulated Kinase Expression in the Dorsal Root Ganglion and Spinal Cord Induced by Colorectal Distension in Rats

BACKGROUND/AIMS: DA-9701, a standardized extract of Pharbitis Semen and Corydalis Tuber, is a new prokinetic agent that exhibits an analgesic effect on the abdomen. We investigated whether DA-9701 affects visceral pain induced by colorectal distension (CRD) in rats. METHODS: A total of 21 rats were divided into three groups: group A (no CRD+no drug), group B (CRD+no drug), and group C (CRD+DA-9701). Expression of pain-related factors, substance P (SP), c-fos, and phosphorylated extracellular signal-regulated kinase (p-ERK) in the dorsal root ganglion (DRG) and spinal cord was determined by immunohistochemical staining and Western blotting. RESULTS: The proportions of neurons in the DRG and spinal cord expressing SP, c-fos, and p-ERK were higher in group B than in group A. In the group C, the proportion of neurons in the DRG and spinal cord expressing p-ERK was lower than that in group B. Western blot results for p-ERK in the spinal cord indicated a higher level of expression in group B than in group A and a lower level of expression in group C than in group B. CONCLUSIONS: DA-9701 may decrease visceral pain via the downregulation of p-ERK in the DRG and spinal cord.

Immunohistochemical localization of calcium binding proteins and some neurotransmitters in myenteric plexus of goat stomach

To understand the neurochemical properties of the gastric myenteric plexus of ruminants, the expression patterns of calbindin D-28k (CB), calretinin (CR), substance P (SP) and calcitonin gene-related peptide (CGRP) were explored in the Korean native goat. In gastric myenteric plexus, CB and SP immunoreactivity were observed in round- or ovalshaped neurons. CR and CGRP immunoreactivity were detected only in the nerve fibers. This immunohistochemical localization of CB, CR, CGRP and SP in the myenteric plexus of the goat stomach exhibited species-specific patterns. These findings suggest that these substances may be directly or indirectly related to the gastric functions of the goat stomach.

Present study on the forensic medicine diagnosis of the sudden erethistic death / 法医学杂志

The death caused of anaphylactic shock is common in clinical medicine and medicolegal expertise, but it is a nodus to diagnose sudden death from allergy. In recent years, to provide objective and precise morphological evidence and index of diagnosis for sudden death from allergy, scholars of internal and overseas studied the content of IgE, HT, mast cell tryptase and SP in the serum of the death died of anaphylactic shock, and their immune express in lung and stomach intestine. In this text we reviewed the present study and existing problems of the forensic medicine diagnosis of the sudden erethistic death.

Expression of substance P in human laryngopharynx and gastrointestine in sudden erethistic death / 法医学杂志

OBJECTIVE@#To study the expression of substance P (SP) in human sudden erethistic death, and to seek objective morphological supports to diagnose sudden erethistic death for forensic medicine.@*METHODS@#The expression of SP was detected with immunohistochemical technique on 15 human laryngopharynx and gastrointestine of sudden erethistic death, and 20 sudden death of heart attack as control. The images of SP were analyzed by image analyzer, and the positive indexes (PI) were calculated.@*RESULTS@#SP expression in the experimental groups was significantly stronger than that in the control one (P < 0.001).@*CONCLUSION@#SP expression can offer an objective morphological reference support for forensic diagnosing sudden erethistic death.

Interaction between substance P and gastrin-releasing peptide on thyrotropin secretion by rat pituitary in vitro

The effect of substance P (SP) on thyrotropin (TSH) secretion is controversial. In this study we evaluated the effect of SP on TSH secretion by hemipituitaries of 3-month-old Wistar rats in vitro and its interaction with gastrin-releasing peptide (GRP) at equimolar concentrations (1 µM and 10 µM). TSH release was measured under basal conditions and 30 min after incubation in the absence or presence of SP, GRP or both peptides. Pituitary TSH content was also measured in the pituitary homogenate after incubation. SP at both concentrations caused a significant (P<0.05) increase in TSH secretion compared with all other groups, which was approximately 60 percent (1 µM) and 85 percent (10 µM) higher than that of the control group (23.3 + or - 3.0 ng/ml). GRP at the lower concentration did not produce a statistically significant change in TSH secretion, whereas at the concentration of 10 µM it produced a 50 percent reduction in TSH. GRP co-incubated with substance P completely blocked the stimulatory effect of SP at both concentrations. Pituitary TSH content decreased in the SP-treated group compared to controls (0.75 + or - 0.03 µg/hemipituitary) at the same proportion as the increase in TSH secretion, and this effect was also blocked when GRP and SP were co-incubated. In conclusion, in an in vitro system, SP increased TSH secretion acting directly at the pituitary level and this effect was blocked by GRP, suggesting that GRP is more potent than SP on TSH secretion, and that this inhibitory effect could be the predominant effect in vivo

Neuropeptide control of the cardiovascular system in fish and reptiles

Accumulating evidence shows the involvement of neuropeptides in cardiovascular control in mammals as well as non-mammalian species. Our own immunohistochemical studies indicate a sparse innervation only in cyclostomes, holostean fish and lungfish, a more extensive variation and distribution in elasmobranchs and teleosts, and a rich and varied innervation of the cardiovascular system in crocodiles and lizards. Vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), gastrin releasing peptide (GRP) and tachykinins are present in most vertebrate groups. VIP is vasodilatory in the Atlantic cod (Gadus morhua) as in most mammalian species, but increases gut vascular resistance in the spiny dogfish (Squalus acanthias). NPY potentiates the effect of noradrenaline on skate (Raja rhina) coronary vessels, suggesting an interaction between adrenergic mechanisms and NPY early in evolution, but studies in the spiny dogfish and the crocodile also demonstrate different mechanisms for the action of NPY and adrenaline in some species. Bombesin/GRP increases flow to the gut in the spiny dogfish by an increase in somatic vascular resistance, while visceral resistance remains unchanged. In the caiman (Caiman crocodylus crocodylus) bombesin causes a shunting of blood from the lung to the gut. Substance P and other tachykinins in general increase flow to the gut, and on some occasions also increase somatic blood flow. Flow in the anastomosis of the crocodile (Crocodylus porosus) gut is increased by substance P. The results presented here are a review of several published and unpublished studies.

Estimulación electrica del sistema nervioso autonomo y descarga de polipeptido intestinal vasoactivo (VIP) y sustancia (SP) sobre el esfinter esofagico inferior (EEI) / Eletric stimulation of the antonomic nervous system and vasoactive intestinal peptide and substance P discharge on the lower esophageal sphincter

Fue investigado el efecto de la estimulación eléctrica de los nervios esplácnicos y vagos sobre la presión del esfínter esofágico inferior (PEEI) y la secreción de VIP y SP en el drenaje venoso del mismo esfínter. Se utilizó el esfínter esofágico porcino aislado in vivo. La integridad funcional de los nervios autónomos fue comprobada por el efecto de la estimulación nerviosa sobre la frecuencia cardíca. La estimulación vagal aumentó la PEEI 8 veces y la secreción de VIP 3 veces, lo que fue estadísticamente significativo (p , 0.01), mientras que la secreción de SP no fue afectada. La estimulación esplácnica aumentó significativamente la frecuencia cardíaca pero no tuvo efecto sobre la secreción de VIP ni SP y no modificó la PEEI. La atropina abolió parcialmente el efecto de la estimulación vagal sobre la PEEI, pero la secreción de VIP fue completamente resistente al bloqueo atropínico. La administración de guanetidina no tuvo ningún efecto sobre la PEEI ni sobre la secreción de VIP y SP tanto durante la estimulación esplácnica como durante la estimulación vagal. Dado que la estimulación vagal aumenta la secreción de VIP en el EEI sacamos como conclusión que VIP actúa como neurotransmisor. Sin embargo, el hallazgo de resistencia parcial a la atropina en la medición de la PEEI y resistencia total en la secreción de VIP y SP, sugiere que otros transmisores participan en la actividad vagal sobre la PEEI