Local release of pro-inflammatory mediators, such as substance P, from afferent neurons causes neurogenic inflammation. The involvement of SP was observed in various animal models of inflammation, including, but not limited to cecal-ligation and puncture induced sepsis 23 , burns injury 67 , and colitis The role of substance P in acute pancreatitis and associated lung injury has been extensively studied.
It was found that in normal mice, substance P and NK1R expression in the pancreas are both increased during caerulein-induced acute pancreatitis 3, Moreover, pancreatitis associated lung injury was almost completely abolished when NK1R or PPTA were knocked out, as shown by reduced intrapulmonary sequestration of neutrophils and pulmonary microvascular permeability 3, 4.
Similar protective effects were observed with hemorrhagic pancreatitis induced by feeding mice a diet deficient in choline, supplemented with ethionine CDE diet in NK1 receptor knockout mice These results showed that PPTA gene products, as well as NK1R, are critical pro-inflammatory mediators in acute pancreatitis and the associated lung injury.
SP-NK1R interaction is also a determinant of inflammatory edema in acute interstitial pancreatitis Furthermore, mice treated with CP96,, a specific NK1R antagonist, either prophylactically or therapeutically, were significantly protected against caerulein-induced acute pancreatitis These results point to a key role of SP-NK1R interaction in acute pancreatitis and associated lung injury.
Primary sensory neurons that innervate the tissues contain an abundance of neurotransmitters, including substance P. Transient receptor potential vanilloid type 1 TRPV1 channels located on these neurons, when activated, causes neuronal release of stored substance P. It was demonstrated in vivo that capsazepine, a TRPV1 antagonist, significantly reduced inflammation and pancreatic injury in caerulein-induced acute pancreatitis On the other hand, activation of TRPV1 by capsaicin caused release of substance P, and exaggerated caerulein-induced acute pancreatitis Pre-treatment of capsazepine or CP96, before administration of capsaicin showed reduced severity of acute pancreatitis, highlighting the importance of TRPV1 and NK1R High doses of Resiniferatoxin caused disruption of the celiac ganglion and inhibited substance P release, and showed protective effects against caerulein-induced pancreatitis in rats A detailed review of the role of TRPV1 in acute pancreatitis is available The effects of substance P can be terminated through enzymatic degradation by neutral endopeptidase NEP.
Genetic deletion of NEP exacerbates pancreatic damage and associated lung injury, and also increased mortality rate in CDE diet induced acute pancreatitis NEP is also a determinant of pancreatic elastase associated lung injury Besides pro-inflammatory effects of substance P in acute pancreatitis, it also mediates nociception in animal models of acute pancreatitis.
Induction of necrotizing pancreatitis by L-arginine caused a large increase in c-fos expressing spinal neurons, suggesting activation of nociceptive pathways. Intrathecal administration of SR, a specific NK1R antagonist, was shown to suppress pancreatitis pain In another study, intraperitoneal injection of CP99,, another specific NK1R antagonist, attenuated nociceptive behaviours in dibutyltin dichloride induced acute pancreatitis Surprisingly there has been little work evaluating the role of substance P in chronic pancreatitis.
Substance P was identified as a mediator of pain responses in chronic pancreatitis. NK1R mRNA levels in chronic pancreatitis patients were significantly correlated with the intensity, frequency and duration of pain A marked increase of substance P contained nerve endings was observed from the inflamed pancreatic tissue, when compared to healthy subjects 8. Gene and peptide expression of substance P has been detected in isolated pancreatic acinar cells.
Expression of substance P can be induced by caerulein, but its physiological significance is unclear 34, On the other hand, exogenous substance P is able to stimulate the expression of chemokines in isolated primary pancreatic acinar cells. The stimulatory effect of substance P was mediated through the NF-kB pathway Substance P has also been shown to regulate pancreatic secretion.
Exogenous substance P dose-dependently inhibited cholecystokinin-induced amylase release and secretin induced juice flow via the pancreatic duct in isolated, perfused rat pancreas These observations were suggested to be mediated by a neural pathway and involve activation of the neurokinin-1 receptor In contrast, Schmidt et al.
It is currently unclear whether the conflicting observations in these two studies are the result of species variation or methodological differences. The effect of substance P on pancreatic secretion was also investigated using pancreatic cells.
In isolated guinea pig pancreatic acinar cells, substance P caused a twofold increase in amylase secretion Experiments done on AR42J cells a rat pancreatic acinar cells line also showed evidence of increased exocrine secretion when these cells were treated with substance P Capsaicin acts by activating TRPV1 channels in the primary ganglia, causing a massive release of stored substance P and then followed by depletion of available substance P.
Capsazepine is a structural analog of capsaicin. There are several commercially available SP antibodies. It is recommendable to test out the antibodies before use. Skip to main content. Search form Search. Koh, Yung Hua, and Bhatia, Madhav. Substance P SP. Gene symbol: Tac1 Homo sapiens , Mus musculus , Rattus norvegicus 1.
Physiological and pathological functions Although the existence of substance P has been known for more than eighty years, the bulk of physiological and pathological roles of SP have been uncovered only in the past 20 years.
Pain One of the earliest physiological functions of substance P is described in its role in nociception. Vomiting The vomiting center in the medulla controls the vomiting reflex. Inflammation Substance P has also been linked with the pathogenesis of inflammatory disorders.
Other functions of substance P Mood disorders, anxiety, stress Substance P was suggested to have anxiogenic properties. Neurogenesis Substance P promotes the proliferation of adult rat neural progenitor cells. Respiratory rhythm 6.
Substance P increases respiratory rhythm and tidal volume. Vasodilation 50 Dermatitis 26 2. Pancreatic Information i. Substance P in acute pancreatitis The role of substance P in acute pancreatitis and associated lung injury has been extensively studied.
Substance P in chronic pancreatitis Surprisingly there has been little work evaluating the role of substance P in chronic pancreatitis. Substance P in pancreatic acinar cells Gene and peptide expression of substance P has been detected in isolated pancreatic acinar cells.
Effects of substance P on pancreatic exocrine secretion Substance P has also been shown to regulate pancreatic secretion.
Tools for study of Substance P a. The mice were healthy and fertile. These mice were protected against caerulein-induced acute pancreatitis. These mice were protected against caerulein-induced acute pancreatitis 3 NEP knockout mice. These mice showed potentiated effects of substance P. It has been used in several acute pancreatitis studies with success 28, 38, L, Compound ID: It has been used in acute pancreatitis with success.
It was shown to suppress pancreatitis pain in L-arginine induced pancreatitis. It was shown to block the inhibitory effect of substance P on exocrine secretion CP99, Compound ID: It was shown to suppress nociceptive behavior in dibutyltin dichloride induced acute pancreatitis Improved fluorophores, better optics and the increased sensitivity of detection systems have led to an increased usage of fluorescently labeled ligands. It is of vital importance that additions of fluorescent groups do not alter the normal functioning of the ligand, for example, by changing the binding affinity or by altering the receptor activation properties of the ligand.
If the fluorescent group does alter the properties of the ligand, it is important that these alterations be understood so that the results obtained with the labeled ligand can be correctly interpreted.
In this study, we have examined the fundamental consequences of labeling the neuropeptide SP with five different fluorescent probes by comparing the effects of the labeled compounds with those of the parent compound, SP. All five of the fluorescent probes were modified at the Lys 3 position with aromatic groups. Alexa and tetramethylrhodamine add negative and positive charges, respectively, to SP.
With regard to size, BODIPY Fl is the smallest of the fluorophores added, whereas Alexa and tetramethylrhodamine are the largest of the fluorophores. The experiments repeatedly showed that Alexa SP does not posses the same characteristics as unlabeled SP. Furthermore, Alexa SP did not exhibit functional activity in two different assays.
Given the importance of Lys 3 in the mouse SPR, it is therefore conceivable that an alteration in the charge of the parent compound, SP, as is the case with Alexa SP and tetramethylrhodamine-SP, may cause a change in the typical actions of SP.
The addition of Alexa causes a greater change in the charge of SP, which might inhibit proper ligand-receptor interaction and thus hinder binding of the SP analog to the SPR.
Tetramethylrhodamine also alters the charge of SP, but unlike Alexa , the fluorophore is positively charged. Therefore, the less drastic charge alteration made by tetramethylrhodamine may allow the mechanistic characteristics of SP to be preserved, albeit with a decreased potency to inhibit I M. Although the structure of fluorescein is very similar to that of Oregon Green 2', 7'-difluorofluorescein , fluorescein-SP did not behave in the same manner as Oregon Green SP or unlabeled SP.
Thus, labeling with either of these two fluorophores did not alter the functional activity of SP at the SPR in either a heterologous expression system or native cells. These might be explained by the differences in the mechanisms that underlie the measurements made in the different experiments.
The binding experiments measure the actions of the peptides at the receptor. The data may reflect the fact that receptor binding and signal activation are not strictly correlated in G-protein coupled systems. Similarly, membrane staining was observed in transfected CHO cells, but not in untransfected cells. Molecular Probes introduced and investigated seven Alexa dyes, including Alexa , and reported that the dyes were more fluorescent and more photostable than their counterparts [ 14 ].
In their study, Alexa was compared to fluorescein. The investigators conjugated the Alexa fluorophores and other similar compounds, such as fluorescein, to different proteins to compare brightness and stability. They showed that Alexa was brighter and more stable than fluorescein when conjugated to biotin binding proteins, goat anti-mouse IgG and its F ab' 2 fragments.
However, they did not test for alterations in binding affinities or biological activity after the addition of the fluorophores. Another study has examined the effects of fluorescent conjugation on opioid peptide activity [ 15 ].
However, when Alexa was conjugated to TIPP and endomorphin, the binding affinities of the parent compounds were decreased. Buku et al. These investigators had previously conjugated the fluorophores to the seventh position of vasotocin, a nonapeptide, and found that it had biological activity, but that the biological activity was reduced when compared to the native compound [ 17 ].
Therefore, the investigators conjugated the fluorophores to the ninth position and found that the analog was fold more potent than the analog with the fluorophores at the seventh position. Thus, they concluded that by moving the bulky fluorophore to the end of vasotocin, and not altering an amino acid involved in binding and activation of the vasotocin receptor minimized the reduction in biological activity of the probes. In summary, our results along with those from other labs show that, in some cases, conjugation of a specific fluorescent label can be added to a peptide without altering the activity of the parent compound.
In other cases, however, the activity of the original compound may be drastically altered. Therefore, the biological activity of each novel fluorophore conjugate must be analyzed. Analysis of labeled compounds should include assessment of binding and biological activity as well as brightness and stability. The results of our study show that there are dramatic differences in the function of SP labeled at the Lys 3 position with different fluorophores. Alexa , which was the largest and added the most charged groups to SP, was unable to label the SPR and altered the biological activity of SP in live and cultured cells.
The chemical formulae for the labeled compounds are shown in Fig. James Krause and maintained as previously described [ 18 ]. The following day, the slides were rinsed with PBS. Two of the three wells from each slide were stained with nM of one of the SP conjugates. The third well of each slide served as a negative control, in that the cells were incubated with PBS in the absence of a SP analog.
The green fluorophores were excited using a FITC fluorescein isothiocyanate filter set excitation nm, dichroic LP, emission nm. The red fluorophore was excited using a TRITC tetramethylrhodamine isothiocyanate filter set excitation nm, dichroic LP, emission nm. All digital images of the green fluorophores were taken at a constant gain 16 and exposure time 0. Pictures of tetramethylrhodamine-SP, the red fluorophore, were taken at a gain of 8 and a 0.
The specificity of the fluorescent staining to the rSPR was analyzed in two ways. First, incubating untransfected CHO cells with nM of each analog assessed non-specific staining.
The cells were rinsed, fixed and viewed as described above. Background, as determined by measuring the intensity and area of 10 control cells incubated with PBS in the absence of a fluorophore, was subtracted. Cell area was used to normalize between cells, thus the ratio of intensity to area was calculated for the treated and untreated cells. Following incubation, cells were filtered and washed using a Millipore vacuum manifold France.
In each experiment, specific binding was determined by subtracting nonspecific binding from the original cpm measurements. The data were plotted as a function of competitor concentration vs. Ionomycin Sigma, St.
Responses are expressed as a fraction of the ionomycin maximum response. Two experiments were carried out to serve as negative controls. Each of the SP isoforms was added to untransfected CHO cells at a concentration of 10 nM and the signals, if any, were recorded. The second control experiment measured fluorescence produced by the SP analogs themselves, in the absence of cells. If a response was observed at a 10 nM concentration, then 0.
Single neurons were dissociated from bullfrog sympathetic ganglia as described previously [ 19 ]. The ganglia were triturated to release single neurons for daily use. Drugs were applied by single cell superfusion [ 20 ] and the bath constantly perfused separately with extracellular solution. Whole cell recordings were made with electrodes with resistances of 0.
The compositions of solutions for electrophysiology are shown in mM unless otherwise noted. Extracellular solution: NaCl , KCl 2. Growth medium: NaCl , KCl 2. I M was monitored by ms pulses from a holding potential of mV to mV every 8 s.
The recordings were filtered at 1 kHz and stored on magnetic tape. The I M relaxations were sampled on line at 2.
Such a detrimental role is also supported by genome-wide linkage studies identifying the TAC1 gene encoding the substance P precursor protein as a possible MS susceptibility gene Vandenbroeck et al.
Together, the available data indicate that interactions between substance P and NK-1R dictate the inflammatory response observed in diverse CNS infections or disorders. Additionally, the amount of substance P released by neurons and immune cells, along with the number of available receptors, determines the level of neuroinflammation, as greater release of substance P permits diffusion of this neuropeptide to more distal binding sites broadening its effect Abbadie et al.
An active immune response can be protective as well as detrimental in the CNS. While infiltrating leukocytes and resident glia play a role in limiting infection and trauma-associated damage, immune responses generated by these events may prove detrimental if not controlled and limited at the appropriate time Douglas and Leeman, Indeed, multiple neurodegenerative disorders are associated with exacerbated immune responses by resident and recruited cells in the brain.
Therefore, a delicate balance needs to be struck in order to limit the generation of damaging inflammation within the CNS.
For some bacterial and viral infections, substance P has been demonstrated to be necessary for clearance. For example, murine gammaherpesvirus 68 has been demonstrated to increase the expression of substance P and its receptor in mucosal and lymphoid organs.
In contrast, this neuropeptide appears to contribute to disease pathology for some infectious agents. For example, substance P increases the bronchoconstriction and damaging cardiac inflammation following infection with respiratory syncytial virus and encephalomyocarditis virus, respectively Bost, b ; Robinson et al.
Likewise, substance P contributes to the severity of inflammation associated with Trypanosoma brucei infection and inflammation and granuloma size in a mouse model of Taenia solium cysticercosis Kennedy et al.
As we discussed earlier, our data suggest that substance P similarly exacerbates damaging inflammation within the CNS to disparate bacterial pathogens. NK-1R null mice and mice treated with an NK-1R antagonist showed reduced inflammatory and maintained immunosuppressive cytokine production, as well as decreased astrogliosis, cellularity and demyelination following intracerebral administration of the Gram negative bacterial pathogens N.
Targeting NK-1R also has the potential to ameliorate CNS disorders that are thought to involve sterile inflammation given the presence of substance P immunoreactive glia in MS plaques Kostyk et al. As such, the available data suggests that substance P contributes to neuroprotection during some degenerative CNS disorders and to beneficial cell-mediated host responses against viruses and intracellular bacteria facilitating pathogen clearance.
In contrast, NK-1R-mediated augmentation of glial and recruited leukocyte immune responses appears to be detrimental during extracellular bacterial and parasite infections of the CNS, and perhaps MS, by exacerbating neuroinflammation and neurological damage as summarized in Table 1.
Table 1. The involvement of tachykinins in a wide range of pathological processes has made them an attractive target for therapeutic intervention, and the pharmaceutical industry has initiated the development of additional NK-1R antagonists as discussed in Quartara and Altamura, ; Quartara et al.
However, the utility of next generation NK-1R antagonists in the treatment of CNS conditions including nausea, addiction, pain, and depression, has been of particular interest due to their ability to cross the blood-brain barrier.
The first NK-1R antagonists were developed in the early s, but most were not effective as analgesics and anti-depressants as they could not efficiently cross the blood-brain barrier. An exception to this rule was LY, which was shown to block rodent licking behavior in the late stages of persistent nociceptive activation with inhibition of ex vivo substance P binding to both peripheral and central NK-1R Iyengar et al.
Subsequently, an analysis of the pharmacokinetics of the non-peptide NK-1R antagonist ezlopitant in dogs revealed the presence of this compound and its two pharmacologically active metabolite compounds in cerebrospinal fluid following intravenous or oral administration, indicating its ability to cross the blood brain barrier Reed-Hagen et al.
Similarly, the NK-1R antagonist casopitant, when radioactively labeled, has been demonstrated to be rapidly absorbed into the bloodstream and can subsequently be found within the brain Ruhlmann and Herrstedt, This antagonist has completed phase II and III clinical trials and has similar success to aprepitant in the treatment of chemotherapy-induced nausea and vomiting Ruhlmann and Herrstedt, , but this drug has not yet received United States Food and Drug Administration approval.
The ability of NK-1R antagonists to cross the blood-brain barrier means that these agents have the potential for use in the treatment in wide range of CNS disorders. Indeed, aprepitant and its pro-drug fosaprepitant are currently employed as post-chemotherapy anti-emetic agents Aapro et al.
Likewise, casopitant has completed phase II and phase III trials and has similar success to aprepitant in the treatment of chemotherapy-induced nausea and vomiting Ruhlmann and Herrstedt, In addition to use as an anti-emetic, there has been promising research that aprepitant and other NK-1R antagonists may have efficacy against other CNS disorders including depression.
The NK-1R antagonist MK has been shown to effectively suppress depressive behavior in guinea pigs, and both MK and casopitant successfully completed phase II clinical trials to treat depression Kramer et al. This hope stems from the promising effects of NK-1R antagonists capable of crossing the blood-brain barrier in animal models of such disorders Table 1. For example, the NK-1R antagonist SR has shown efficacy as a co-therapy with other anti-inflammatory agents in ameliorating myelin oligodendrocyte glycoprotein-induced EAE, a mouse model of MS Reinke et al.
Similarly, CP , has also been demonstrated to reduce EAE severity, and this effect was associated with stabilization of the blood brain barrier as well as reduced T-helper type 1 immunity Nessler et al. For example, since direct hippocampal substance P administration elicits seizures in mice and an NK-1R antagonist has been shown to prevent seizure activity in a rodent model of helminth brain infection Robinson et al.
Furthermore, our own studies have shown that pharmacological targeting of NK-1R with the antagonist L, can not only prevent the development of damaging inflammation due to streptococcal CNS infection when administered prophylactically, but can also reverse infection-associated gliosis and demyelination when delivered therapeutically without increasing CNS bacterial burden Chauhan et al.
While further studies are clearly needed to define the specific mechanisms underlying the ability of substance P to augment CNS inflammation and its role in pathogen clearance, the available data raise the intriguing possibility that currently approved NK-1R antagonists, such as aprepitant, could be repurposed for use as a co-therapy to limit neuroinflammatory damage associated with infectious agents and certain neurodegenerative conditions.
The use of such agents might have considerable advantages over other anti-inflammatory agents such as corticosteroids, non-steroidal anti-inflammatory drugs, prostaglandin inhibitors, and P2X7 antagonists, by limiting excessive inflammation without broadly attenuating host immune responses that may be required to resolve infection. Continued research on the ability of NK-1R antagonists to alleviate these health conditions may therefore yield new treatment options for patients with CNS infections, and perhaps other inflammatory neurological disorders.
Infectious and sterile CNS disorders are often associated with overwhelming and damaging inflammation due to the immune responses of resident CNS cells and infiltrating leukocytes. Currently, neuroinflammatory diseases such as meningitis are treated with corticosteroids in combination with antibacterial, antiviral, or antifungal agents Aberdein and Singer, ; Hoffman and Weber, Corticosteroids have both anti-inflammatory and immunosuppressive properties and treatment with these agents has been shown to reduce the risk of hearing loss and mortality due to meningitis.
However, the immunosuppressive properties of corticosteroids may interfere with the ability of the body to clear infections, especially if the antibiotics used are not effective or antiviral medications are not available Fitch and van de Beek, Furthermore, corticosteroid treatment can lead to adverse effects including the development of ulcers, myopathy, and bone loss, or central effects including sleep disorders and mood swings.
As such, there is a current need for new treatment options to limit neuroinflammation associated with infection of the CNS and neurodegenerative conditions. Substance P is produced at high levels in the CNS, and its target receptor NK-1R is expressed by resident CNS cells including microglial and astrocytes, and by immune cells that can infiltrate the CNS such as macrophages and lymphocytes.
Importantly, this tachykinin functions both as a neurotransmitter and an immunomodulator, and substance P is recognized to exacerbate inflammatory responses at peripheral sites including the skin, lung and gastrointestinal and urogenital tracts. Our own studies indicate that therapeutic intervention with NK-1R antagonists can limit neuroinflammation, reactive gliosis and demyelination in a mouse model of streptococcal meningitis Chauhan et al.
This data therefore supports the use of NK-1R receptor antagonists in the treatment of such neuroinflammatory disorders. Figure 1. Substance P-mediated exacerbation of neuroinflammatory damage following central nervous system CNS infection. Local inflammation promotes the recruitment of leukocytes to the site of infection that will, in turn, recognize microbial components and produce more pro-inflammatory and neurotoxic mediators.
Importantly, inflammatory cytokines can also augment the expression of PRR and NK-1R by glia and leukocytes, and can elevate local production of substance P. This positive feedback loop would be anticipated to increase the sensitivity of host cells to pathogen components and sensitize leukocytes and glia to this neuropeptide, thereby exacerbating inflammatory damage.
Intervention with pharmaceutical NK-1R inhibitors capable of penetrating the blood-brain barrier would prevent substance P mediated exacerbation of glial and leukocyte inflammatory responses, and interrupt such a feedback loop. The latest generation of NK-1R antagonists can be delivered orally and can readily cross the blood-brain barrier.
Importantly, these antagonists exert central effects and the NK-1R antagonist, aprepitant, is approved for use as an anti-emetic agent in patients receiving chemotherapy.
As such, the repurposing of currently available NK-1R antagonists may yield alternative co-therapy options for CNS inflammation associated with extracellular bacteria and parasites, and perhaps MS, with more specificity and reduced adverse effects.
All authors have contributed significantly to the preparation of this review article. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Aapro, M. Aprepitant and fosaprepitant: a year review of efficacy and safety. Oncologist 20, — Abbadie, C. Spinal cord substance P receptor immunoreactivity increases in both inflammatory and nerve injury models of persistent pain.
Neuroscience 70, — Aberdein, J. Clinical review: a systematic review of corticosteroid use in infections. Care Agro, A. Inhibition of murine intestinal inflammation by anti-substance P antibody. PubMed Abstract Google Scholar. Andoh, T. Brain Res. Arsenescu, R. IL induction of mRNA encoding substance P in murine macrophages from the spleen and sites of inflammation.
Baker, S. Cloning of a C-terminally truncated NK-1 receptor from guinea-pig nervous system. Beaujouan, J. NK-1 receptors are the only class of tachykinin receptors found on mouse cortical astrocytes.
Peptides 12, — Beinborn, M. U S A , — Benarroch, E. Depletion of ventromedullary NK-1 receptor-immunoreactive neurons in multiple system atrophy. Brain , — Human positron emission tomography studies of brain neurokinin 1 receptor occupancy by aprepitant. Psychiatry 55, — Bernstein, C. Bettelli, E. Reciprocal developmental pathways for the generation of pathogenic effector T H 17 and regulatory T cells.
Nature , — Bill, A. Substance P: release on trigeminal nerve stimulation, effects in the eye. Acta Physiol. Blum, A. Interleukin 12 and antigen independently induce substance P receptor expression in T cells in murine schistosomiasis mansoni. Bost, K. Quantification of macrophage-derived substance P receptor mRNA using competitive polymerase chain reaction. Tachykinin-mediated modulation of the immune response. Tachykinin-modulated anti-viral responses. Substance P: a late-acting B lymphocyte differentiation cofactor.
Bradesi, S. Role of spinal microglia in visceral hyperalgesia and NK1R up-regulation in a rat model of chronic stress. Gastroenterology , Brown, G.
Inflammatory neurodegeneration and mechanisms of microglial killing of neurons. Caberlotto, L. Neurokinin 1 receptor and relative abundance of the short and long isoforms in the human brain.
Calvo, C. Substance P enhances IL-2 expression in activated human T cells. Castagliuolo, I. Neurokinin-1 NK-1 receptor is required in Clostridium difficile- induced enteritis. Chauhan, V. Vesicular stomatitis virus infects resident cells of the central nervous system and induces replication-dependent inflammatory responses. Virology , — Prophylactic and therapeutic targeting of the neurokinin-1 receptor limits neuroinflammation in a murine model of pneumococcal meningitis.
NOD2 plays an important role in the inflammatory responses of microglia and astrocytes to bacterial CNS pathogens. Glia 57, — Neurogenic exacerbation of microglial and astrocyte responses to Neisseria meningitidis and Borrelia burgdorferi. Chen, L. Drug Targets 5, — Chernova, I. Corrigan, F. Inflammation in acute CNS injury: a focus on the role of substance P. Covas, M. Disturbed immunoregulatory properties of the neuropeptide substance P on lymphocyte proliferation in HIV infection.
Croitoru, K. Selective modulation of the natural killer activity of murine intestinal intraepithelial leucocytes by the neuropeptide substance P. Immunology 71, — Cuello, A. Detection of substance P in the central nervous system by a monoclonal antibody. U S A 76, — The distribution of substance P immunoreactive fibers in the rat central nervous system.
Organization of substance P primary sensory neurons: ultrastructural and physiological correlates. Cunningham, S. DeFea, K. Cell Biol. Di Fabio, R. Identification, biological characterization and pharmacophoric analysis of a new potent and selective NK1 receptor antagonist clinical candidate.
Douglas, S. AIDS Res. Retroviruses 24, — Neurokinin-1 receptor expression and function in human macrophages and brain: perspective on the role in HIV neuropathogenesis. N Y Acad. Elevated substance P levels in HIV-infected men. AIDS 15, — Neurokinin-1 receptor: functional significance in the immune system in reference to selected infections and inflammation. Doyle, C. Substance P receptor neurokinin-1 -expressing neurons in lamina I of the spinal cord encode for the intensity of noxious stimulation: a c-Fos study in rat.
Neuroscience 89, 17— Ebner, K. The role of substance P in stress and anxiety responses. Amino Acids 31, —
0コメント