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

The common acute lymphoblastic leukemia antigen (CALLA) is a 749-amino acid type II integral membrane protein expressed by most acute lymphoblastic leukemias, certain other lymphoid malignancies with an immature phenotype, and normal lymphoid progenitors. A computer search against the most recent GenBank release (no. 56) indicates that human CALLA cDNA encodes a protein nearly identical to the rat and rabbit neutral endopeptidase 24.11 ("enkephalinase;" EC 3.4.24.11). This zinc metalloendopeptidase, which has been shown to inactivate a variety of peptide hormones including enkephalin, chemotactic peptide, substance P, neurotensin, oxytocin, bradykinin, and angiotensins I and II, had not been identified in lymphoid cells. To determine whether CALLA cDNA derived from human acute lymphoblastic leukemia cells (Nalm-6 cell line) encodes functional neutral endopeptidase activity, we generated CALLA+ stable transfectants in the CALLA- murine myeloma cell line J558 and analyzed them for enzymatic activity in a fluorometric assay based upon cleavage of the substrate glutaryl-Ala-Ala-Phe 4-methoxy-2-naphthylamide at the Ala-Phe bond. Total lysates as well as whole-cell suspensions of the Nalm-6 line and of the CALLA+ transfectants, but not of the CALLA- J558 cells, possessed neutral endopeptidase activity. This enzymatic activity was associated with the cellular membrane fraction and was abrogated by the specific neutral endopeptidase inhibitor phosphoramidon. The unequivocal identification of CALLA as a functional neutral endopeptidase provides insight into its potential role in both normal and malignant lymphoid function.
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PMID:Common acute lymphoblastic leukemia antigen (CALLA) is active neutral endopeptidase 24.11 ("enkephalinase"): direct evidence by cDNA transfection analysis. 252 88

The chicken Harderian gland, the major lacrimal gland, has two major cell populations: a cortical secretory epithelium and a medullary interstitial cell population of lymphoid cells. There is an extensive acetylcholinesterase (AChE) network throughout the gland, as well as catecholamine positive fibers among the interstitial cells. There are substance P-like (SPLI) and vasoactive intestinal polypeptide-like (VIPLI) immunoreactive fibers throughout the gland. These fibers are particularly dense and varicose among the interstitial cells. The adjacent pterygopalatine ganglion complex has neuronal somata that exhibit VIPLI and were AChE-positive. This ganglion complex also contains SPLI and catecholamine-positive fibers. In regions of the ganglion, the somata appear surrounded by SPLI varicosities. Surgical ablation of the ganglion eliminated or reduced the VIPLI, AChE and catecholamine staining in the gland. The SPLI was reduced only in some regions. Ablation of the superior cervical ganglion or severance of the radix autonomica resulted in the loss of catecholamine staining in the pterygopalatine ganglion and the gland. Severance of the ophthalmic or infraorbital nerves had no effect on the VIPLI or the SPLI staining pattern in the gland.
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PMID:Neuropeptides and the innervation of the avian lacrimal gland. 274 5

By the use of light microscopic (LM) immunohistochemistry the distribution of tachykinin (TK)-, calcitonin gene-related peptide (CGRP)- and neuropeptide Y (NPY)-like immunoreactivity in nerves supplying the mammalian (rat, mouse, guinea-pig, cat) thymus gland has been determined. There were no interspecies variations. Fibres staining for TK and CGRP completely overlapped indicating coexistence. They were present in the capsule, in interlobular septa and in the corticomedullary boundary and occurred in perivascular and paravascular plexus supplying arteries, veins and the microvasculature. Some TK/CGRP-immunoreactive (ir) fibres travelled between lymphoid cells and close contacts with mast cells were frequent. NPY-ir fibres were different from those staining for TK/CGRP and predominated in the perivascular plexus of arterial blood vessels. Only very rarely they coursed in the lymphoid parenchyma. Intimate contacts of NPY-ir fibres with mast cells were less frequent than those of TK/CGRP-ir fibres. We conclude that the NPY innervation is mainly sympathetic noradrenergic while thymic nerves coding for TK and CGRP are most likely of sensory origin. These pathways may play a differential neuroimmunomodulatory role in the thymus, possibly via interaction with mast cells.
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PMID:Tachykinins, calcitonin gene-related peptide and neuropeptide Y in nerves of the mammalian thymus: interactions with mast cells in autonomic and sensory neuroimmunomodulation? 278 55

Rats were injected with capsaicin at 1-2 days of age to abolish the content of substance P (SP) in nerve terminals. At 6 weeks of age the capsaicin-treated and control rats were sensitized daily for 1 or 2 subsequent weeks Monday through Friday with ovalbumin (OA). The OA was given without adjuvant as 300 ng subcutaneous (s.c.) injections in the neck region or as 1% aerosol for 30 min. The capsaicin-treated animals which were sensitized s.c. for 2 weeks reacted moderately with increased transpulmonary pressure (TPP) to airway challenge with OA, and strongly to intravenous (i.v.) challenge with OA or serotonin. The capsaicin-untreated animals, which were sensitized with OA, reacted weakly to the challenge. In the challenge. In the animals sensitized with aerosolized OA, slightly lower reactivity was seen compared with those sensitized s.c. Untreated and unsensitized control rats reacted only to serotonin challenge. No animal had any detectable serum or bronchial IgE antibodies. Aerosol-sensitized animals had IgG antibodies in both serum and bronchial lavage. Histologically, the animals treated with capsaicin in contrast to the untreated controls demonstrated a pronounced increase of lymphoid tissue around their bronchi. Their mast cell numbers were increased around vessels and in the pleura and their mucous cell numbers were increased in the epithelium of the bronchi and bronchioli. The sensitization did not add much to this histological picture.
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PMID:Enhancement of the bronchial reactivity in immunized rats by neonatal treatment with capsaicin. 372 96

Using a sensitive and specific reverse transcribed-polymerase chain reaction (RT-PCR), it was possible to quantify relative increases in preprotachykinin (PPT) mRNA expression in vivo following oral administration of Salmonella. Despite the presence of constitutive levels of PPT mRNA expression in the Peyer's patches, expression of this mRNA increased within 20 h following oral administration of Salmonella. Increases in PPT mRNA expression were also detected in both the mesenteric lymph nodes and spleens following Salmonella administration despite the lack of constitutive PPT mRNA expression in these lymphoid organs. Furthermore, mononuclear leukocytes contributed to this increased expression of PPT mRNA, suggesting that the initial immune response against Salmonella occurs in the presence of increased tachykinin expression.
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PMID:Inducible preprotachykinin mRNA expression in mucosal lymphoid organs following oral immunization with Salmonella. 749 93

Experimental data strongly suggest that the nervous and immune systems are interrelated. One example of this interrelation is anatomical and is represented by innervation of the lymphoid organs by substance P (SP) immunoreactive fibers, among others. Neurotransmitters/neuropeptides can exert functional receptor-mediated immunologic responses. SP binding to its receptor induces cytokine production in macrophages and T cells and stimulates IgG secretion from B cells. SP has also been associated with inflammation and other immune-mediated diseases such as arthritis. We have previously reported an in vitro stimulatory effect of SP on hematopoiesis that was mediated mostly by the induction of two relevant hematopoietic growth factors, IL-3 and granulocyte-macrophage-CSF (GM-CSF). In this study, we have shown that SP, through the carboxyl terminus, induces the production of IL-3 and GM-CSF in bone marrow mononuclear cells. This production requires de novo synthesis and is blocked by two different SP-R antagonists, spantide and CP-96,345-1. The induction of IL-3 and GM-CSF is partially mediated by IL-1 and IL-6, which are also produced by bone marrow mononuclear cells. Furthermore, the production of IL-3 and GM-CSF correlated with an accumulation of their respective steady state mRNAs. T cells found within the bone marrow are responsible for most of the induced IL-3. Because SP mediates the release of IL-1, IL-3, IL-6, and GM-CSF, all important hematopoietic regulators, by bone marrow cells, this study further suggests the possibility of a regulatory role of the nervous system in hematopoiesis mediated by neuropeptides such as SP.
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PMID:Induction of IL-3 and granulocyte-macrophage colony-stimulating factor by substance P in bone marrow cells is partially mediated through the release of IL-1 and IL-6. 751 64

The presence of substance P (SP) and vasoactive intestinal peptide (VIP) in auricular lymph nodes of normal and sensitized guinea pigs and mice has been investigated using polyclonal antibodies directed against these neurotransmitters and the unlabelled peroxidase-antiperoxidase procedure. Positive immunoreactivity could be observed only in draining lymph nodes of sensitized animals. SP-immunoreactivity was found in mice and guinea pigs but a VIP-positive reaction only in mice. The immunopositive sites were always associated with blood vessels. The present study suggests that the neurotransmitters SP and VIP are involved in mechanisms of sensitization taking place in secondary lymphoid organs.
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PMID:Immunohistochemical detection of substance P and vasoactive intestinal peptide fibres in the auricular lymph nodes of sensitized guinea pigs and mice. 751 73

Previous reports have described the ectopic expression of substance P binding sites on lymphoid aggregates and small blood vessels in inflammatory bowel disease. In this report, three non-peptide NK-1 receptor antagonists, CP-96,345, RP-67,580, and L-703,606 abolished saturable 125I-Bolton-Hunter substance P binding to the ectopically expressed receptors in frozen sections of surgically resected bowel from five patients with either Crohn's disease or ulcerative colitis. The rank order of affinity was approximately substance P approximately CP-96,345 approximately L-703,606 > RP-67,580. These results suggest that: (i) the ectopically expressed substance P binding sites in inflammatory bowel disease are authentic NK-1 receptors, (ii) all ectopically expressed receptors on small blood vessels, and lymphoid aggregates as well as normally expressed receptors on the bowel circular muscle have similar receptor affinities and specificities for substance P and the non-peptide antagonists, and (iii) non-peptide antagonists may be therapeutically beneficial in inflammatory bowel disease by inhibiting the pro-inflammatory effects of substance P acting via the NK-1 receptor.
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PMID:Substance P binding sites on intestinal lymphoid aggregates and blood vessels in inflammatory bowel disease correspond to authentic NK-1 receptors. 752 13

A number of anatomical studies have demonstrated the presence of peptidergic nerve fibers infiltrating mucosal lymphoid tissues. The exact mechanisms of how neuropeptides are released to affect these lymphoid sites are unclear, but radiolabeled binding studies have shown that mucosal leukocytes bear a number of neuropeptide receptors on their cell surfaces capable of responding to neural signals. The presence of neuropeptide-containing fibers and the ability to receive neural signals suggest that mucosal lymphocytes can be influenced by neurogenic mediators. The objectives set forth in this review are to provide what is currently known about the ability of substance P and vasoactive intestinal peptide to promote mucosal IgA responses in the gastrointestinal tract via Th2 mechanisms and to discuss how these neuropeptides contribute to the exacerbation of the inflammatory diseases of the gastrointestinal tract. We describe how immune responses develop in the gastrointestinal immune system and emphasize how neuropeptides may influence the differentiation of lymphocytes in mucosal inductive tissues and their subsequent expression in mucosal effector sites. Finally, we discuss new techniques developed by the Mucosal Immunization Research Group that have enabled the study of mucosal immune responses.
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PMID:The enteric nervous and immune systems: interactions for mucosal immunity and inflammation. 753 Nov 2

This study examined the distribution of peptidergic nerve fibers in Peyer's patches to determine whether appropriate receptors were present. Vasoactive intestinal peptide (VIP), substance P (SP), calcitonin gene-related peptide (CGRP) and receptors for VIP and SP were localized in lymphoid follicles of the cat ileum using a combined indirect horseradish peroxidase and streptavidin-biotin method. The margins of follicles were innervated by nerve fibers containing VIP, SP and CGRP. Nerve fibers were predominantly around lymphatics and high endothelial venules at the edges of follicles. Specific receptors for VIP and SP were present at the margins of follicles and in the lamina propria around crypts. VIP receptors were numerous on T cells within and around high endothelial venules and lymphatic vessels and at the margins of follicles. SP receptors were identified on a small number of T and B cells, granulocytes and macrophages, restricted to the margins of follicles. The defined distribution in ileal lymphoid tissue of nerve fibers containing VIP and SP and the corresponding localization of their appropriate receptors support immunoregulatory roles for neuropeptides in mucosal immunity.
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PMID:Immunohistochemical localization of peptidergic nerve fibers and neuropeptide receptors in Peyer's patches of the cat ileum. 753 34


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