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)

The gastro-intestinal tract is highly innervated by both intrinsic and extrinsic sensory nerves and this neuronal component is thought to play a role in local inflammatory responses. This in vivo study was designed to determine the function of substance P and the tachykinin NK1 receptor in the pathogenesis of inflammatory bowel disease by the use of the specific antagonist RP 67580. The dinitrofluorobenzene (DNFB)-induced colonic hypersensitivity model is associated with increased levels of substance P in the colon. The tachykinin NK1 receptor antagonist RP 67580 was used to investigate the role of substance P on the development of diarrhea, mast cell infiltration and activation, colonic tissue damage, hypertrophy of colonic lymphoid structures and leukocyte infiltration. The formation of watery diarrhea could completely be abrogated by treatment with RP 67580 in DNFB-sensitized animals 72 h after challenge. Antagonizing the tachykinin NK1 receptor in these animals also resulted in significantly reduced colonic patch hypertrophy, leukocyte recruitment and tissue damage. Total levels of substance P in the colon of DNFB-sensitized mice treated with the inactive enantiomer of the tachykinin NK1 receptor antagonist were significantly higher compared to DNFB-sensitized mice treated with RP 67580 72 h after challenge. Although RP 67580 was capable of reducing the total number of mast cells present in the colon, mast cell activation was not affected by this treatment. In conclusion, in this chemically-induced immunological model for inflammatory bowel disease we demonstrated an important role for tachykinin NK1 receptors, and its ligand substance P, in the development of colitis downstream from mast cell activation.
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PMID:Beneficial effect of tachykinin NK1 receptor antagonism in the development of hapten-induced colitis in mice. 1694 72

The nervous system in the intestine controls motility, secretion, sensory perception, and immune function. Peptidergic neurones with neurotransmitters such as substance P and nerve growth factors have been the main focus of neuroimmunomodulation research in the gut. This review summarises the present knowledge concerning the role of the sympathetic nervous system (SNS) in modulating intestinal inflammation. The role of the SNS for gut inflammation is compared with its role in rheumatoid arthritis which demonstrates notable similarities. Nerve fibres of the SNS not only enter the enteric plexuses but also innervate the mucosa and gut associated lymphoid tissue (GALT). The SNS has pro- and anti-inflammatory functions. Neurotransmitters such as norepinephrine, adenosine, and others can evoke remarkably different opposing effects depending on concentration (presence of sympathetic nerve fibres and extent of neurotransmitter release), receptor affinity at different receptor subtypes, expression of adrenoceptors, availability of cotransmitters, and timing of SNS activity in relation to the inflammatory course. This review attempts to integrate the different perspectives of the pro- and anti-inflammatory effects of the SNS on inflammatory disease of the gut.
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PMID:The role of the sympathetic nervous system in intestinal inflammation. 1704 10

Psychoneuroimmunology is a relatively new field of study that investigates interactions between behaviour and the immune system, mediated by the endocrine and nervous systems. The immune and central nervous system (CNS) maintain extensive communication. On the one hand, the brain modulates the immune system by hardwiring sympathetic and parasympathetic nerves (autonomic nervous system) to lymphoid organs. On the other hand, neuroendocrine hormones such as corticotrophin-releasing hormone or substance P regulate cytokine balance. Vice versa, the immune system modulates brain activity including sleep and body temperature. Based on a close functional and anatomical link, the immune and nervous systems act in a highly reciprocal manner. From fever to stress, the influence of one system on the other has evolved in an intricate manner to help sense danger and to mount an appropriate adaptive response. Over recent decades, reasonable evidence has emerged that these brain-to-immune interactions are highly modulated by psychological factors which influence immunity and immune system-mediated disease.
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PMID:Psychoneuroimmunology--cross-talk between the immune and nervous systems. 1750 36

The Ikaros (Ik) gene encodes alternatively spliced zinc-finger proteins originally identified in developing hematopoietic organs and acts as master regulator of lymphoid development. During our search for transcription factors that control the developmental expression of the enkephalin (ENK) gene we found that Ik-1 and Ik-2 isoforms are specifically expressed in the embryonic striatum and bind the Ik-like cis-regulatory DNA element present on the ENK gene. Ik proteins are expressed by both proliferating (BrdU+/nestin+) and by post-mitotic differentiating (MAP2+) cells in the developing striatum between embryonic day 12 and post-natal day 2 and mRNAs encoding for the Ik and ENK genes are co-expressed by a subset of differentiating striatal neurons. Blocking the DNA binding of Ik proteins in differentiating embryonic striatal neuronal cultures resulted in decreased ENK expression and mutant animals lacking the DNA-binding domain of Ik had a deficit in the number of ENK but not in dynorphin or substance P mRNA+ cells. Animals lacking the protein interaction domain of Ik showed no deficit. These results demonstrate that Ik-1 and Ik-2 proteins through their DNA binding act as positive regulators of ENK gene expression in the developing striatum and participate in regulating enkephalinergic differentiation.
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PMID:Ikaros is expressed in developing striatal neurons and involved in enkephalinergic differentiation. 1750 64

In the decades before 1987, most of the research devoted to neuronal innervation was carried out in primary and secondary lymphoid organs at very different locations. This was an important period in order to understand hard-wiring of immune organs in physiology. Between 1988 and 1997, with the appearance of specific antibodies against neuronal markers, innervation was studied in inflamed tissue of patients and of animals with autoimmune diseases. This period clearly revealed that nerve fibers of, both, the sympathetic and sensory nervous system are altered, but only small amounts of tissue have been investigated by qualitative but not quantitative techniques. Between 1998 and 2007, with the understanding that sympathetic and sensory neurotransmitters might play opposite roles in inflammation, nerve fibers of the different nervous systems have been studied in parallel using quantitative techniques. These studies have been carried out in a large number of patients with long-standing autoimmune diseases. It turned out that sympathetic nerve fibers are lost in chronically inflamed tissue, while substance P-positive nerve fibers sprout into the inflamed area. This might be important because high concentrations of sympathetic neurotransmitters are antiinflammatory whereas substance P has a proinflammatory role. The first challenge for future research is the determination of innervation in the early human autoimmune disease. The second challenge is the identification of reasons for the differential loss of sympathetic in relation to sensory nerve fibers. It might well be that nerve repellent factors specific for the sympathetic nerve fiber might play an important role for the observed differential loss. Whether, or not, a therapy can be based on these findings remains to be established.
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PMID:Autoimmune disease and innervation. 1751 88

In this work we have examined the appearance and distribution of nitric oxide synthase (NOS), with histochemical, immunohistochemical and biochemical methods, during development of the sea bass (Dicentrarchus labrax) gut. The data showed that both the calcium-calmodulin dependent neuronal isoform (nNOS) and calcium-independent inducible isoform (iNOS) are present in the larval gut of sea bass. The nNOS-immunoreactivity was present in the epithelial cells and enteric nerve cells of gut both in the 8-day-old specimens and in the 24-day-old-larvae. In the adult nNOS-immunoreactivity disappeared from epithelial cells, remaining in the wall intramural neurons and fibers. The iNOS-immunoreactivity was present in the epithelial cells of 24-day-old-larvae and was not detectable in the adult gut. Western blot analysis and determination of NOS activity also demonstrated the presence of the two NOS isoforms, nNOS and iNOS, in the gut of 24-day-old specimens. The presumably different roles played by the two isoforms of enzyme are discussed. The presence of nNOS isoform in the gut enteric neurons of the same larval stages of D. labrax in which we previously demonstrated the presence of substance P and Vasoactive Intestinal Polypeptide (VIP), may suggest that all these three components of the motility control system are already present in the larval phase. Nitric oxide (NO) may be also involved in the early immune response. The present results on the occurrence of iNOS isoform in epithelial gut cells of the same regions in which the gut-associated lymphoid tissue (GALT) will differentiate, may suggest for NO a role in early defence mechanisms, before the establishment of immune responses in GALT. Finally, the developmental and regional differences in nNOS and iNOS expression also suggest a regulatory role in development and differentiation of the sea bass gut.
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PMID:Occurrence of two NOS isoforms in the developing gut of sea bass Dicentrarchus labrax (L.). 1761 32

The function of lymphoid organs and immune cells is often modulated by peptides and hormones produced by the neuroendocrine and immune systems. We have previously reported the intrathymic expression of neuropeptides in the thymus of different species and that neuropeptides can influence murine thymocyte development in vitro. To further explore the evolutionary nature of neuroendocrine interactions in the thymus, we identified the expression of calcitonin-gene-related peptide, neuropeptide Y, somatostatin (SOM), substance P and vasointestinal polypeptide, as well as their receptors on chicken thymic epithelial cells (TEC) and thymocytes by immunofluorescence and reverse transcription polymerase chain reaction (RT-PCR). All the studied neuropeptides and their receptors were found to be expressed in both TEC and thymocytes, suggesting that intrathymic neuroendocrine interactions may take place within the avian thymus. In order to elucidate whether such interactions play a role in avian thymocyte development, neuropeptides and their antagonists were added to embryonic thymus organ cultures and found to influence chicken thymopoiesis. In particular, an antagonist of SOM increased the proportion of double-positive thymocytes, while SOM itself appeared to inhibit the early stages of thymocyte development. Taken together, these data provide further evidence to suggest that neuropeptides play a conserved role in vertebrate thymocyte development.
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PMID:Functional analysis of neuropeptides in avian thymocyte development. 1789 98

Substance P (SP) is a neuropeptide associated with sensory innervation of lymphoid tissue and a suspected modulator of lymphatic function in inflammation. Only a few studies have examined the effects of SP on lymphatic contraction, and it is not clear to what extent SP acts directly on the lymphatic muscle and/or endothelium or indirectly through changes in intraluminal filling pressure secondary to increases in capillary permeability/filtration. We tested the effects of SP on the spontaneous contractions of rat isolated mesenteric lymphatic vessels under isometric and isobaric conditions, hypothesizing that low concentrations would stimulate lymphatic pumping by enhancing lymphatic muscle contraction in a manner complementary to the effect of increased preload. Under isometric conditions, SP (10 nM) dramatically enhanced lymphatic chronotropy and inotropy. Unlike guinea pig lymphatics, SP actions were not blocked by cyclooxygenase or PLA(2) inhibition. In the absence of SP, ramp increases in isometric preload resulted in x approximately 1.6 increases in contraction amplitude (Amp) and x approximately 1.7 increases in frequency (Freq). SP increased Freq by x approximately 2.4, Amp by x approximately 1.9, and the Amp-Freq product (AFP) by x approximately 3.5. Under isobaric conditions, the pressure elevation from 0.5 to 10 cmH(2)O in the absence of SP decreased Amp by x approximately 0.6 and increased Freq by x approximately 1.8. SP caused a modest increase in Amp, a robust increase in Freq at all pressures, and shifted the AFP-pressure relationship upward and leftward. Therefore, SP has substantial positive inotropic and chronotropic effects on rat lymphatic muscle, improving pump efficiency independent of the effects of preload and broadening of the working range of the lymphatic pump.
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PMID:Modulation of lymphatic muscle contractility by the neuropeptide substance P. 1853 52

Palatine tonsils (PTs), together with ileal Peyer's patches, rank among the first colonization sites for infectious prions. After replicating in these lymphoid tissues, prions undertake the process of "neuroinvasion," which is likely mediated by the peripheral nerves connecting lymphoid tissues to the central nervous system (CNS). To study the connections between the tonsils and the CNS, we injected fluorescent tracers into the PTs of lambs; the highest number of Fast Blue (FB)-labeled neurons was found in cranial cervical ganglia (CCG), whereas a progressively decreasing number of cells were detected in proximal glossopharyngeal, proximal vagal, trigeminal, pterygopalatine, and cervicothoracic ganglia. Immunohistochemistry was carried out on tonsil and ganglia cryosections. Immunoreactivity (IR) for tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), neuronal nitric oxide synthase (nNOS), calcitonin gene-related peptide (CGRP), substance P (SP), and calcium-binding protein S100 (S100), was observed in the fibers around and within PT lymphoid nodules. In the trigeminal, proximal glossopharyngeal and vagal ganglia the retrogradely-labeled neurons showed nNOS-, SP- and CGRP-IR. In all ganglia some retrogradely-labeled neurons showed nNOS-, SP- and CGRP-IR co-localization. It is worth noting that only 66+/-19% and 75+/-13% of retrogradely-labeled neurons in CCG showed TH- and DBH-IR, respectively. The present results allow us to attribute PT innervation mainly to the sympathetic component and to the glossopharyngeal, vagal and trigeminal cranial nerves. Furthermore, these data also provide a plausible anatomic route through which infectious agents, such as prions, may access the CNS, i.e. by traveling along several cranial and sympathetic nerves, as well as by migration via glial cells.
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PMID:Characterization of sheep (Ovis aries) palatine tonsil innervation. 1936 24

Hemokinin 1 (HK-1) is a substance P-like tachykinin peptide predominantly expressed in non-neuronal tissues. In addition to a prominent function in lymphoid development, recent studies indicate a potential role for HK-1 in immunoregulation. The current study was focused on its action on mature B cells. Despite the negligible effect on its own, HK-1 exhibited a profound influence on B cell activation elicited by several classical signals, including LPS stimulation, BCR cross-linking, and CD40 ligation. Cells therefore showed enhanced proliferation, survival, and CD80/86 expression, and produced more IgM with a higher frequency of Ab-forming cells. Biochemical analysis revealed that HK-1 alone was sufficient to induce the activation of MAPKs and the expression of Blimp-1 and Xbp-1 in B cells. Nevertheless, costimulation with a known B cell activator resulted in much enhanced phosphorylation of MAPKs and transcriptional activation of Blimp-1 and Xbp-1. Overall, these data support that HK-1 provides an important costimulatory signal for B cell activation, possibly through synergistic activation of the MAPK pathway and induction of transcription factors critical for plasmacytic differentiation.
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PMID:Hemokinin-1 activates the MAPK pathway and enhances B cell proliferation and antibody production. 2020 12


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