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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The peptides of the tachykinin family are widely distributed within the mammalian peripheral and central nervous systems and play a well-recognized role as excitatory neurotransmitters. Currently, the concept that tachykinins act exclusively as neuropeptides is being challenged, since the best known members of the family, substance P, neurokinin A and neurokinin B, are also present in non-neuronal cells and in non-innervated tissues. Moreover, the recently cloned mammalian tachykinins hemokinin-1 and endokinins are primarily expressed in non-neuronal cells, suggesting a widespread distribution and important role for these peptides as intercellular signaling molecules. The biological actions of tachykinins are mediated through three types of receptors denoted NK(1), NK(2) and NK(3) that belong to the family of G protein-coupled receptors. The identification of additional tachykinins has reopened the debate of whether more tachykinin receptors exist. In this review, we summarize the current knowledge of tachykinins and their receptors.
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PMID:Tachykinins and tachykinin receptors: a growing family. 1472 95

Many of the stromal-derived signals and factors that regulate B lymphopoiesis have been identified. We review recent evidence from our laboratory that shows that there are at least three phases during B-cell development when cells direct their own maturation, independent of stromal cells. Following the expression of the preB-cell receptor (preBCR), cells acquire the ability to proliferate in low levels of interleukin-7 (IL-7), which acts as a self-selecting mechanism to expand cells that have successfully expressed a preBCR in environments that are non-permissive to preBCR- cells. Second, the preBCR is required for a contact-mediated event between B-cell progenitors. Disruption at this stage prevents the further maturation of progenitors to the lipopolysaccharide (LPS)-responsive stage. Finally, the transition from IL-7 receptor to mature antigen receptor-based signaling is enhanced by a novel member of the tachykinin family, hemokinin-1. This series of maturation, survival, and differentiation signals is generated by B-lineage cells as they progress through developmental checkpoints on the way to becoming functionally mature cells.
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PMID:Mechanisms of selection mediated by interleukin-7, the preBCR, and hemokinin-1 during B-cell development. 1496 88

Granulomas are chronic inflammations that prevent spread of poorly controllable infectious agents. The gut lumen contains enteric organisms that are excluded from the host by leukocytes located in the intestinal lining. Physiological intestinal inflammation and granulomas share some similarities. Both function to confine, but not necessarily abolish potentially harmful factors. Also, both are subject to intense immune regulation to avoid unnecessary tissue injury. Substance P and its natural analog hemokinin are produced at these sites of inflammation and are important components of this regulatory process. They act through a shared receptor (NK-1) expressed on T cells, macrophages, dendritic cells and probably other cell types. One of their functions is to enhance IFN-gamma production and amplify the Th1 response. The NK-1 receptor is an important target for immune regulation. Several Th1 cytokines and T cell antigen receptor (TCR) activation induce NK-1 receptor expression on T cells, while IL-10 and TGF-beta block receptor display. Macrophages also have an inducible NK-1 receptor. Various types of immune cells can make substance P and hemokinin, whose syntheses also are subject to immunoregulation. Thus, substance P and hemokinin are inflammatory cytokines with overlapping functions that help control immune responses in granulomas and at mucosal surfaces, and probably elsewhere.
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PMID:The role of substance P, hemokinin and their receptor in governing mucosal inflammation and granulomatous responses. 1497 99

Evidence has been mounting for peripheral functions for tachykinins, a family of neuropeptides including substance P (SP), neurokinin A, and neurokinin B, which are recognized for their roles in the central and peripheral nervous system. The recent discovery of 4 new members of this family, the endokinins (EKA, B, C, and D), which are distributed peripherally, adds support to the notion that tachykinins have physiologic/endocrine roles in the periphery. In the present study we report a fundamental new function for tachykinins in the regulation of platelet function. We show that SP stimulates platelet aggregation, and underlying this is the intracellular mobilization of calcium and degranulation. We demonstrate the presence of the tachykinin receptors NK1 and NK3 in platelets and present evidence for the involvement of NK1 in SP-mediated platelet aggregation. Platelets were found to contain SP-like immunoreactivity that is secreted upon activation implicating SP-like substances in the autocrine/paracrine regulation of these cells. Indeed, NK1-blocking antibodies inhibited aggregation in response to other agonists. Of particular note is the observation that EKA/B cross-react in the SP immunoassay and are also able to stimulate platelet activation. Together our data implicate tachykinins, specifically SP and EKA/B, in the regulation of platelet function.
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PMID:Tachykinins regulate the function of platelets. 1513 Sep 44

Substance P (SP) belongs to the tachykinin family of molecules. SP, cleaved from preprotachykinin A, is a neuropeptide and a proinflammatory leukocyte product. SP engages neurokinin 1 receptor (NK-1R) to stimulate cells. Hemokinin (HK) is another tachykinin that binds NK-1R. HK comes from preprotachykinin C, which is distinct from preprotachykinin A. We determined whether HK functions like SP at inflammatory sites. Preprotachykinin C mRNA was in murine schistosome granulomas and intestinal lamina propria mononuclear cells. Granuloma T cells and macrophages expressed preprotachykinin C mRNA. HK bound granuloma T cell NK-1R with high affinity. SP and HK stimulated IFN-gamma production with equal potency. NK-1R antagonist blocked the effect of SP and HK on IFN-gamma secretion. Thus, both HK and SP are expressed at sites of chronic inflammation and share cell origin, receptor, and immunoregulatory function. Two distinct but functionally overlapping tachykinins govern inflammation through NK-1R at sites of chronic inflammation.
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PMID:Cutting edge: hemokinin has substance P-like function and expression in inflammation. 1515 65

The mammalian tachykinins are a family of peptides that, until recently, has included substance P (SP), neurokinin A and neurokinin B. Since, the discovery of a third preprotachykinin gene ( TAC4), the number of tachykinins has more than doubled to reveal several species-divergent peptides. This group includes hemokinin-1 (HK-1) in mouse and rat, endokinin-1 (EK-1) in rabbit, and EKA, EKB, human HK-1 (hHK-1) and hHK(4-11) in humans. Each exhibits a remarkable selectivity and potency for the tachykinin NK(1) receptor similar to SP. Their peripheral expression has led to the proposal that they are the endogenous peripheral SP-like endocrine/paracrine agonists where SP is not expressed. Moreover, their strong cross-reactivity with a specific SP antibody leads us to question many of the proposed locations and roles of SP in the periphery. Additionally, three orphan tachykinin gene-related peptides are identified on TAC4, in rabbit, EK-2 and in humans, EKC and EKD.
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PMID:Hemokinins and endokinins. 1522 88

Mammalian tachykinins are traditionally viewed as neuropeptides. This review describes the mammalian tachykinins and evidence for expression of these peptides by non-neuronal cells. Tachykinin expression is defined as evidence for gene transcription, peptide production, or peptide secretion. Since the functions of mammalian tachykinins have been amply reviewed, the biological roles of these peptides will be noted briefly, with emphasis on immune cell action. Of particular interest is the predicted existence and non-neuronal expression of new mammalian tachykinins--hemokinin 1, the endokinins and C14TKL-1. Synthetic forms of these peptides have high affinity for the NK1 receptor, the protein traditionally associated with substance P binding. By acting on the same "substance P" receptor, these tachykinins have the potential for promoting similar post-receptor functions. The structure and action of representative non-mammalian tachykinins acting on mammals are also presented. These peptides, of interest in their own right, also appear to exhibit selectivity for the NK1 receptor. They strengthen the notion that multiple ligands may be capable of binding to one receptor, NK1, effecting similar cellular responses.
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PMID:Non-neuronal mammalian tachykinin expression. 1535 78

Tachykinins represent a family of neuropeptides sharing similar C-terminus sequences, but exhibiting preferential binding to one of three receptors called neurokinin receptors (NK-R). While known for its role in contracting smooth muscle or acting as a pain signal neurotransmitter, substance P (SP) and other tachykinins can directly influence immune responses. Studies from the early 1980s revealed that human lymphocytes bore NK-R, but it remains unclear, even to-date, why such receptors are expressed on leukocytes. Nerve tracing studies have provided some speculation that the nervous system can assist the immune system in stimulating an immune response dependent upon which neuropeptide-bearing fibers infiltrate specific lymphoid structures. Such observations have important implications for regulating mucosal responses given that tachykinin-bearing nerve fibers extensively innervate the gut, and SP concentrations in the gut are second only to the brain. Such evidence suggests that SP and related neuropeptides may be important in controlling bacterial infections of the gut. This is shown by blocking SP action in which mice show increased susceptibility to Salmonella infections since induction of IFN-gamma is significantly reduced. In addition, the absence or its presence of SP's or the newly discovered lymphocyte-derived neurokinin called hemokinin's action can modify host IgA responses. Thus, tachykinins introduce new circuits to immune regulation suggesting that these neuropeptides exhibit cytokine- and chemokine-like action.
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PMID:The role of tachykinins on bacterial infections. 1535 50

The aim of this study was to analyze the function and expression of tachykinins, tachykinin receptors, and neprilysin (NEP) in the mouse uterus. A previous study showed that the uterotonic effects of substance P (SP), neurokinin A (NKA), and neurokinin B (NKB) in estrogen-treated mice were mainly mediated by the tachykinin NK1 receptor. In the present work, further contractility studies were undertaken to determine the nature of the receptors mediating responses to tachykinins in uteri of late pregnant mice. Endpoint and real-time quantitative RT-PCR were used to analyze the expression of the genes that encode the tachykinins SP/NKA, NKB, and hemokinin-1 (HK-1) (Tac1, Tac2, and Tac4); and the genes that encode tachykinin NK1 (Tacr1), NK2 (Tacr2), and NK3 (Tacr3) receptors in uteri from pregnant and nonpregnant mice. The data show that the mRNAs of tachykinins (particularly NKB and HK-1), tachykinin receptors, and NEP are locally expressed in the mouse uterus, and their expression changes during the estrous cycle and during pregnancy. The tachykinin NK1 receptor is the predominant tachykinin receptor in the nonpregnant and early pregnant mouse and may mediate tachykinin-induced uterine contractions in the nonpregnant mouse. The tachykinin NK2 receptor is predominant in the late pregnant mouse and is the main receptor mediating uterotonic responses to tachykinins at late pregnancy. The tachykinin NK3 receptor is expressed in considerable amounts only in uteri from nonpregnant diestrous animals, and its physiological significance remains to be clarified.
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PMID:Functional and molecular characterization of tachykinins and tachykinin receptors in the mouse uterus. 1564 54

The genomes of extant vertebrates have been shaped by a series of whole genome and individual gene duplication events. The 2R hypothesis, which postulates that two whole genome duplications occurred in relatively rapid succession very early in chordate evolution, is gaining increasing acceptance. A further entire genome duplication is believed to have occurred in the ancestral fish lineage approximately 320-350 Myr ago, as well as more recent independent tetraploidization events, mostly but not exclusively, in particular teleost and amphibian lineages. Superimposed upon these whole genome duplications are tandem or segmental duplications of individual genes or groups of genes that have taken place at different rates in the various vertebrate lineages. The majority of duplicated genes become pseudogenes or are deleted but some may evolve to encode components with new functional roles. Genes encoding members of neuropeptide Y- and tachykinin-families are associated with the HOX-bearing chromosomes and these systems provide examples of duplication events that have led to rapid evolution of the duplicated gene which has occasionally produced peptides, such as pancreatic polypeptide, seminalplasmin and hemokinin-1, with new biological functions.
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PMID:The evolution of neuroendocrine peptides. 1586 48


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