Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As part of an ongoing investigation of human mast cell heterogeneity, we have isolated, partially purified, and characterized the uterine mast cell and compared it with mast cells isolated from other organs. The average histamine content of myometrium and leiomyofibroma obtained from hysterectomies was 2.1 +/- 0.3 (mean +/- SEM) microgram/g of tissue (n = 10), and the histamine content of the two tissues did not differ significantly. A mild collagenase, hyaluronidase, and DNase digestion was used to disperse the uterine mast cells, with an average yield of 9.5% (range, 0 to 21%). The average histamine/uterine mast cell was 2.1 +/- 0.2 pg (n = 3), and 61 +/- 7% (n= 3) of the uterine mast cells survived overnight culture. Early purification efforts with Percoll gradients have yielded up to 80% pure uterine mast cells, with an average of 27 +/- 10% (n = 5). Uterine mast cells released histamine in response to the secretogogues anti-IgE and A23187 but did not respond to substance P or to the basophil secretogogues FMLP, C5a, and 12-O-tetradecanoylphorbol-13-acetate. After 1 microgram/ml anti-IgE stimulation, the uterine mast cell appeared to make significant quantities of PGD2 (89 +/- 26 ng/10(6) cells, n = 6) (p less than 0.05), as assayed by RIA. Simultaneously, leukotriene C4 release was 45 +/- 15 ng/10(6) cells, (n = 6) (p less than 0.05), as assayed by RIA. Combined gas-chromatography mass spectroscopy analysis of anti-IgE-stimulated cell supernatants confirmed the production of PGD2. In pharmacologic studies, isobutyl-methylxanthine and isoproterenol blocked anti-IgE-induced histamine release. The uterine mast cell is similar to the lung mast cell in terms of response to secretogogues and release of arachidonic acid metabolites. Ultrastructurally, the uterine mast cell contains scroll granules, crystal granules, combined granules, homogeneously dense granules, and large lipid bodies, many with focal lucencies within them. Particle granules, most frequently present in gut mast cells of mucosal origin, were absent from uterine mast cells. Although certain features are analogous to the ultrastructure of skin or lung mast cells, the combination of structures is distinctive for uterine mast cells.
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PMID:Human uterine mast cells. Isolation, purification, characterization, ultrastructure, and pharmacology. 171 65

The sensory neuropeptides, substance P and calcitonin gene-related peptide, have been implicated in inflammatory reactions in several tissues. An immune-complex model of colitis was used in rabbits to determine the colonic content (nmol/g protein) of immunoreactive substance P and calcitonin gene-related peptide at various times after induction of inflammation to assess changes in these neuropeptides during the inflammatory response. Calcitonin gene-related peptide content was decreased by 66% 4 hours after induction of inflammation and reached a maximum of 80% at 48 hours. The substance P content was decreased at 8 hours, with a maximum decrease of 64% at 48 hours. Substance P decrease was detected in the muscle layer. The amounts of substance P in the mucosal/submucosal layer extracts were too low to allow accurate measurements. Calcitonin gene-related peptide decreased both in the muscle and the mucosal-submucosal layers. Immunohistochemical analysis showed that calcitonin gene-related peptide and substance P innervation patterns were comparable in normal and inflamed colon, even though there appeared to be a decrease in density and intensity of the staining, particularly for calcitonin gene-related peptide at 48 hours. The early decrease of calcitonin gene-related peptide and substance P during the time course of colitis might be due to release from nerve terminals of the gut during the inflammatory response. The profound changes in colonic calcitonin gene-related peptide and substance P content during colitis may have important implications during inflammation and subsequent tissue repair and may also lead to disturbances in gut motility.
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PMID:Calcitonin gene-related peptide and substance P decrease in the rabbit colon during colitis. A time study. 171 6

Motor neurons which innervate the circular muscle layer of the guinea-pig small intestine were retrogradely labelled, in vitro, with the carbocyanine dye, DiI, applied to the deep muscular plexus. By combining retrograde tracing and immunohistochemistry, the chemical coding of motor neurons was investigated. Five classes of neuron could be distinguished on the basis of the co-localization of immunoreactivity for the different antigens; the five classes were also characterized by different lengths and polarities of their axonal projections and by their cell body shapes. Two classes with local or orally directed axons were immunoreactive for choline acetyltransferase and substance P and are likely to be cholinergic excitatory motor neurons. Two other classes had anally directed axons; they were immunoreactive for vasoactive intestinal polypeptide and are likely to be inhibitory motor neurons. A small proportion of neurons with short projections to the circular muscle were immunoreactive for neither substance P nor for vasoactive intestinal polypeptide, but are likely to be cholinergic. The morphological and histochemical identification of excitatory and inhibitory motor neurons provides a neuroanatomical basis for the final motor pathways involved in the polarized reflex motor activity of the gut.
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PMID:Identification and immunohistochemistry of cholinergic and non-cholinergic circular muscle motor neurons in the guinea-pig small intestine. 172 Feb 29

This study was designed to assess temporal changes in concentrations of neuromodulatory peptides in plasma and gastrointestinal tissues after in vivo neural isolation of the entire canine jejunoileum. Fasting plasma and transmural biopsy specimens of stomach, duodenum, jejunum, ileum, and colon were obtained from the same dogs before and two, six, and 12 weeks after in situ neural isolation of the entire jejunoileum. Concentrations of vasoactive intestinal peptide, substance P, and neuropeptide Y were determined by quantitative radioimmunoassay. Tissue concentrations of vasoactive intestinal peptide and substance P in the neurally isolated regions increased progressively with time (198% and 217% average maximal increases, respectively), while fasting plasma concentrations changed little. Neuropeptide Y concentrations in plasma and in the jejunoileum were decreased (by 30% to 70%) at two weeks and remained decreased thereafter. Temporal changes in tissue neuropeptide concentrations occur in the neurally isolated jejunum and ileum. These adaptive changes in the neuropeptidergic innervation of the gut may play a role in the alterations in enteric function that occur after extrinsic denervation and after intestinal transplantation.
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PMID:In vivo neural isolation of the canine jejunoileum: temporal adaptation of enteric neuropeptides. 172 99

Despite continued research, the pathophysiologic mechanism responsible for functional obstruction in the aganglionic segment of bowel in Hirschsprung's disease remains controversial. Narrowing of the affected segment is thought by many investigators to be the result of loss of intrinsic inhibitory innervation. For this hypothesis to be consistent, inhibitory neuropeptides should be present in the dilating, transitional segment of bowel. In order to quantitate reported changes in peptidergic nerve staining in Hirschsprung's disease, we measured concentrations of five neuropeptides (vasoactive intestinal peptide, peptide histidine-methionine, met5-enkephalin, substance P and bombesin-like immunoreactivity) by radioimmunoassay in the affected segments of bowel from six patients with Hirschsprung's disease. Tissue extracts were prepared using gut obtained at surgery from the: (1) constricted, aganglionic segment, (2) dilating, aganglionic transitional segment and (3) dilated, proximal ganglionic segment. Concentrations of vasoactive intestinal peptide, peptide histidine-methionine, substance P and met5-enkephalin were significantly reduced in both the muscularis externa and the mucosal-submucosal layers from the constricted aganglionic segment. By contrast, concentrations of the candidate inhibitory neuropeptides, vasoactive intestinal peptide and peptide histidine-methionine, were minimally reduced in the dilating, aganglionic transitional segment. These results are consistent with the hypothesis that constriction of the aganglionic segment is due to loss of intrinsic inhibitory innervation. Concentrations of bombesin-like immunoreactivity were similar in the three segments of human gut, suggesting the presence of this immunoreactive neuropeptide in extrinsic nerve fibers.
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PMID:Segmental distribution of colonic neuropeptides in Hirschsprung's disease. 172 67

Adult rainbow trout (Oncorhynchus mykiss) were injected intraperitoneally with capsaicin, substance P, serotonin, or a control of saline vehicle or bovine serum albumin (0.5 microgram/g body weight). Fish were sacrificed 30 min and 1, 2, and 4 h post-injection, the gut was dissected out, and a small section of the upper intestine was processed for electron microscopy. A significant proportion of eosinophilic granule cells (EGCs) of the intestine were in close association with non-myelinated neuronal bundles in all fish (4 fish per treatment and time period), but there was no significant difference between treatment or time, suggesting that the association was unaffected by these factors. Close examination of EGC ultrastructure showed that fish treated with capsaicin and substance P exhibited limited degranulation of the EGCs in the stratum compactum and extensive crinophagic-like degranulation in the lamina propria. Cells of the lamina propria contained characteristic multivesicular-like bodies. The degranulation was reminiscent of both mast cell degranulation and endocrine cell crinophagy. EGCs of fish treated with serotonin or a control were unaffected, suggesting that the serotoninergic neurons, believed to be involved in gut motility, were not responsible for degranulation. It is apparent that EGCs of the trout intestine may be under nervous control, as has been demonstrated previously for mammalian mast cells.
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PMID:Degranulation of eosinophilic granule cells induced by capsaicin and substance P in the intestine of the rainbow trout (Oncorhynchus mykiss Walbaum). 172 61

This investigation was performed to determine whether antisera raised against microtubule-associated proteins, i.e. MAP1 and MAP2, may constitute an alternative to the silver-impregnation studies for the identification of the distinct morphological enteric neuronal cell types in the porcine small intestine. MAP1-immunostaining seems less suited since it preferentially stains the neuronal somata and axons and hardly permits to observe the dendritic processes. MAP2-immunostaining chiefly visualizes the perikaryal-dendritic domain and the proximal part of the axonal processes in the enteric neurons of the porcine gut. Hence, MAP2-immunostaining enables for the first time the unambiguous immunocytochemical identification of enteric multi(short)dendritic uniaxonal type I neurons. Double labelling techniques using antisera against MAP2 and substance P indicate that part of the type I neurons in the myenteric plexus of the porcine small intestine, which are taking part in an ascending pathway, are substance P-immunoreactive, whereas the substance P/neuromedin U-minineurons in the Meissner's plexus do not stain for MAP2. We may conclude that, although MAP2-immunostaining falls short of the quality achieved with silver-impregnation, the possibility to combine MAP2-immunostaining with neuropeptide immunocytochemistry to study the intestinal neurons has the advantage that part of the enteric neuron types stained with a distinct neurotransmitter or neuromodulator can be classified morphologically.
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PMID:Immunohistochemical visualization of the nervous system in the porcine small intestine using antisera raised against the cytoskeletal proteins MAP1 and MAP2, in combination with neuropeptide immunocytochemistry. 172 68

The bowel is the only organ of the body in which neural reflexes can be elicited in the absence of input from the brain or spinal cord. This activity is mediated by the enteric nervous system (ENS), which contains primary afferent neurons. Experiments were carried out to locate the primary afferent neurons of the ENS. Two types of stimulation were used to activate neurons in the wall of the gut in vitro: exposure of the mucosa to cholera toxin or delivery of pressure to the mucosal surface with puffs of N2 from a micropipette. Neurons that became active in response to these stimuli were identified by demonstrating the intranuclear immunoreactivity of Fos, the product of the c-fos protooncogene. No Fos immunoreactivity could be detected in the absence of stimulation; however, application of cholera toxin and puffs of N2 each induced the appearance of Fos immunoreactivity in neurons in both the submucosal and myenteric plexuses. With either stimulus, the induction of Fos immunoreactivity was antagonized by TTX and therefore depended on neuronal activity. The appearance of Fos immunoreactivity could also be prevented by the 5-HT1P receptor antagonist N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan amide. In contrast, the stimulus-induced expression of Fos immunoreactivity was inhibited, but not abolished, by hexamethonium, which limited the spread of activation within the submucosal plexus and completely prevented expression of Fos immunoreactivity by myenteric neurons in response to mucosal puffs of N2. FluoroGold was injected into single ganglia of the myenteric plexus in order to identify submucosal neurons with myenteric projections. Submucosal neurons in which Fos immunoreactivity was induced by the stimuli were doubly labeled by FluoroGold. A subset of the submucosal, but not myenteric, neurons that expressed Fos immunoreactivity was doubly labeled by antibodies to calbindin. Submucosal calbindin-immunoreactive neurons were found to contain substance P immunoreactivity and could also be immunostained by anti-idiotypic antibodies that react with 5-HT1P receptors. A subset of dynorphin1-8-immunoreactive submucosal neurons (which are known to costore vasoactive intestinal peptide and to be secretomotor in function) expressed nuclear Fos immunoreactivity in response to cholera toxin, but not puffs of N2. These data suggest that intrinsic primary afferent neurons are located in the submucosal plexus, project to the myenteric plexus, and are activated by 5-HT acting on the 5-HT1P receptor subtype. These neurons are probably cholinergic and costore calbindin and substance P.
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PMID:Identification and stimulation by serotonin of intrinsic sensory neurons of the submucosal plexus of the guinea pig gut: activity-induced expression of Fos immunoreactivity. 172 36

The effect of sepsis on plasma levels of various gut peptides was studied in rats. Sepsis was induced by cecal ligation and puncture (CLP); control animals underwent sham operation. Sixteen hours after CLP or sham operation, portal and systemic blood was drawn, and plasma levels of gastrin, vasoactive intestinal peptide (VIP), secretin, peptide YY (PYY), gastrin-releasing peptide (GRP), and substance P were determined by radioimmunoassay. Plasma levels of gastrin, VIP, PYY, and secretin were elevated in septic rats compared with nonseptic animals, with the highest levels noted in portal blood. There was no effect of sepsis on GRP or substance P levels. In other experiments, human recombinant interleukin 1 alpha (IL-1 alpha) or recombinant tumor necrosis factor alpha (TNF alpha) was injected intraperitoneally (300 micrograms/kg body weight in 3 divided doses over 16 hours). There was no change in plasma levels of gut peptides after IL-1 alpha injection. TNF alpha induced elevation of PYY levels in portal plasma with no change in other gut peptide levels. The results suggest that sepsis stimulates release of certain gut peptides and that TNF, but not IL-1, may be partly responsible for this response. The mechanism of the release of gut peptides and its significance in the pathophysiologic changes induced by sepsis remain to be determined.
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PMID:Effect of sepsis or cytokine administration on release of gut peptides. 173 67

Bombesin-like immunoreactivity is present in nerve fibers projecting to the cardiovascular system, including the coronary arteries, and to the gastrointestinal canal, and in endocrine cells of the gut of skates belonging to the family Rajidae. Synthetic bombesin contracted isolated coronary rings from the longnose skate, Raja rhina, in a cumulative fashion. The contractile response was 84% of that of 60 mM potassium chloride. The pD2-value for bombesin was 8.83 (S.E.M. = 0.33; n = 15). Phentolamine, atropine and two substance P-antagonists increased the sensitivity to bombesin, while atenolol, sotalol, nifedipine, tetrodotoxin and two bombesin antagonists were devoid of significant effects. We conclude from this study that a bombesin-like peptide is present in nerves innervating the cardiovascular system and the gastrointestinal canal of skates of the family Rajidae, and that bombesin contracts coronary vessels in vitro via a direct mechanism and/or via mechanisms involving alpha-adrenergic and muscarinergic receptors.
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PMID:Bombesin-like immunoreactivity in skates and the in vitro effect of bombesin on coronary vessels from the longnose skate, Raja rhina. 175 76


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