Human lymphocytes lack substance P receptors (original) (raw)
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Immunomodulatory Properties of Substance P: The Gastrointestinal System as a Model
Annals of the New York Academy of Sciences, 2006
Communication between nerves and immune and inflammatory cells of the small and large intestine plays a major role in the modulation of several intestinal functions, including intestinal motility, ion transport, and mucosal permeability. Neuroimmune interactions at intestinal sites have been associated with the pathophysiology of infectious and enterotoxin-mediated diarrhea and intestinal inflammation, including inflammatory bowel disease (IBD). During the past 20 years the neuropeptide substance P (SP) has been identified as an important mediator in the development and progress of intestinal inflammation by binding to its high-affinity neurokinin-1 receptor (NK-1R). This peptide, released from enteric nerves, sensory neurons, and inflammatory cells of the lamina propria during intestinal inflammation, participates in gut inflammation by interacting, directly or indirectly, with NK-1R expressed on nerves, epithelial cells, and immune and inflammatory cells, such as mast cells, macrophages, and T cells. SP-dependent activation of these cells leads to the release of cytokines and chemokines as well as other neuropeptides that modulate diarrhea, inflammation, and motility associated with the pathophysiology of several intestinal disease states. The recent development of specific nonpeptide NK-1R antagonists and NK-1R-deficient mice helped us understand the functional importance of the SP-NK-1R system in mediating intestinal neuroimmune interactions and to identify the particular cells and signaling pathways involved in this response. This review summarizes our understanding on the immunomodulatory properties of SP and its receptor in the intestinal tract with particular focus on their involvement in intestinal physiology as well as in the pathophysiology of several intestinal disease states at the in vivo and cell signaling level.
Effects of substance P on human colonic mucosa in vitro
American Journal of Physiology-Gastrointestinal and Liver Physiology, 1999
Previous studies indicated that the peptide substance P (SP) causes Cl−-dependent secretion in animal colonic mucosa. We investigated the effects of SP in human colonic mucosa mounted in Ussing chamber. Drugs for pharmacological characterization of SP-induced responses were applied 30 min before SP. Serosal, but not luminal, administration of SP (10−8 to 10−6 M) induced a rapid, monophasic concentration and Cl−-dependent, bumetanide-sensitive short-circuit current ( I sc) increase, which was inhibited by the SP neurokinin 1 (NK1)-receptor antagonist CP-96345, the neuronal blocker TTX, the mast cell stabilizer lodoxamide, the histamine 1-receptor antagonist pyrilamine, and the PG synthesis inhibitor indomethacin. SP caused TTX- and lodoxamide-sensitive histamine release from colonic mucosa. Two-photon microscopy revealed NK1(SP)-receptor immunoreactivity on nerve cells. The tyrosine kinase inhibitor genistein concentration dependently blocked SP-induced I sc increase without impairin...
Immunoregulatory activity of substance P fragments
Molecular Immunology, 1990
The C-terminal SP'-" pentapeptide (Phe-Phe-Gly-Leu-Met-NH,) was found to suppress in citro the immune response in a dose of l-5 pg/ml. It produced also a distinct immunosuppression in oiro. by both per OS and intraperitoneal, applications. In contrast, the N-terminal SPld fragment (Arg-Pro-Lys-Pro) suppressed the response at a dose of 0.1 pg/ml, but stimulated it slightly at higher doses (l-5 pgg/ml). A structural analog of SP'+ (Gly-PreArg-Pro tetrapeptide) was found to be a strong immunosuppressor at a dose of 5 pgg/ml, indicating the importance of N-terminal basic residue for the immunoregulatory activity of intact SP
Immunoregulatory effects of neuropeptides. Stimulation of interleukin-2 production by substance P
Journal of Neuroimmunology, 1992
Substance P (SP), a tachykinin neuropeptide, has been previously reported to stimulate T cell proliferation, and SP receptors have been identified on subpopulations of T lymphocytes. The effect of SP on the interleukin-2 (IL-2) production has been investigated by using the murine EL-4.IL-2 and LBRM-T6G T cell lines. SP synergized with phorbol 12-myristate 13-acetate (PMA) in a dose-dependent manner to induce IL-2 production. The generated interleukin was identified as IL-2 by neutralization with a specific anti-murine IL-2 monoclonal antibody. The effect of SP was specific, since spantide and physalaemin which have affinity for SP receptors inhibited the generation of IL-2 by SP. These results provide additional evidence for the immunoregulatory role of neuropeptides, and suggest that the immunostimulatory action of SP could be mediated, at least in part, through the upregulation of 1L-2 expression.
Neuropeptide substance P and the immune response
Cellular and molecular life sciences : CMLS, 2016
Substance P is a peptide mainly secreted by neurons and is involved in many biological processes, including nociception and inflammation. Animal models have provided insights into the biology of this peptide and offered compelling evidence for the importance of substance P in cell-to-cell communication by either paracrine or endocrine signaling. Substance P mediates interactions between neurons and immune cells, with nerve-derived substance P modulating immune cell proliferation rates and cytokine production. Intriguingly, some immune cells have also been found to secrete substance P, which hints at an integral role of substance P in the immune response. These communications play important functional roles in immunity including mobilization, proliferation and modulation of the activity of immune cells. This review summarizes current knowledge of substance P and its receptors, as well as its physiological and pathological roles. We focus on recent developments in the immunobiology of...
European Journal of Pharmacology, 1988
Intracellular recordings were made from myenteric neurons of the guinea-pig duodenum and the responses to local ejection of several substance P (SP) analogs were examined. It was found that senktide (succinyl-[Asp6,Me-Phe 8 ]SP-(6-11)), a selective analog for the NK-3 (SP-N) receptor, was particularly effective in depolarizing the neurons. It was 20-100 times more potent than SP and about 1000-fold more potent than the selective analogs for the NK-1 (SP-P) receptor, which resides on muscle cells. The response to the peptides was prolonged (20-120 s), but in about 20% of the cells there was a fast, early depolarizing component (observed only with senktide). In most cases there was an increase in the input resistance of the cell during the slow depolarization. Together with the finding that the response reversed at about -90 mV, this indicates that the response is due to the closure of K + channels. The results support the existence of an NK-3 (SP-N) receptor and provide direct information about the membrane mechanisms through which NK-3 agonists excite myenteric neurons.
Journal of Neuroimmunology, 1993
The neuropeptide substance P (SP) has been shown to play an important role as a mediator of neurogenic inflammation. Moreover, in vitro SP is capable of modulating the activity of lymphocytes, monocytes and polymorphonuclear cells. We have examined one of the early events that occur after addition of SP to human peripheral blood mononuclear cells (PBMC). Addition of 10-°-10 -4 M SP to human peripheral blood mononuclear cells results in a dose-dependent rise in intracellular calcium concentration as determined by FACS analysis. We show that the effect of SP cannot be attenuated by the SP receptor antagonist [D-Proa,D-TrpT'9]-SP(4-11), indicating that the response is not mediated via a SP receptor. Amphiphilic peptides like SP appear to have the capacity to insert themselves into the cell membrane and interact directly with intracellu[ar proteins. This hypothesis is supported by the fact that the amphiphilic analogue of SP, [D-Pro2,D-PheT,D-TrpO]-SP, is capable of inducing a calcium response in our system, although it is known as an SP receptor antagonist. Functionally, we show that SP increases the proliferative response of T cells induced by suboptimal concentrations of the mitogen PHA. These data provide evidence of a potential role of SP in the regulation of lymphocyte activation.
Immunohistochemical Localization of Substance P in Mouse Gut
Elsevier eBooks, 1977
The objectives of this study was to provide a quantitative analysis of calcium-binding proteins, calbindin (CB), parvalbumin (PA), substance P (SP), calcitonin gene-related peptide (CGRP) and galanin (GAL), in trigeminal ganglia of goats, to establish whether they exhibit coexistence relationships between each other, and to examine possible colocalization with SP, CGRP and GAL, which have been well characterized according to their distributions in an abundance of large and/or small neurones. CB (12.78%), PA (31.91%), SP (24.63%), CGRP (44.44%) and GAL (3.29%) immunoreactive (IR) cells were observed. About 38.37, 8.7 and 0.73% of CGRP-IR neurones in the trigeminal ganglion were also immunoreacted with SP, GAL and CB, respectively. Almost all SP-IR cells are labelled with CGRP (approximately 92.52%), whereas only 16.02 and 0.44% of SP-IR neurones colocalized with GAL and CB. Approximately 4.65 and 1.10% of the CB-IR cells were found to contain CGRP and SP immunoreactivity, respectively. Conversely, no CB-IR cell exhibited GAL immunoreactivity. In addition, all the GAL-IR cells showed CGRP and SP immunoreactivity. The number of CB-, PA-, SP-, CGRP-and GAL-IR neurones in goat trigeminal ganglion are abundant than that of other animals. These results elucidate that the goat differs from other mammalian species in the distribution and localization of neurochemical substances in trigeminal ganglia, and suggest that this difference may be relevant to the morphological characteristics of cerebral vasculatures such as epidural rete mirabile of goat.