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)

Recent works have shown that the neuropeptide, substance P, is an important element of the central nervous system, functioning as a neurotransmitter as well as moderating neural development. In a previous communication, we provided indirect evidence that substance P played a role in the pathogenesis and pathophysiology of spina bifida by showing an elevation of CSF substance P concentrations in affected foetuses and babies. In this study, we investigated directly the occurrence of substance P in spinal cord tissues in spina bifida and compared it to that found during normal development. Using radioimmunoassay, concentrations of substance P were measured in the spinal cords of 20 normal human foetuses (aged 9-21 weeks) and 4 foetuses with spina bifida (aged 17-19 weeks). Substance P was detected in substantial amounts in the normal foetal spinal cord as early as 9 weeks' gestation, and there was progressive accumulation with age: mean concentrations +/- S.E.M. in 3 subgroups were 56.3 +/- 4.9 pmol g-1 (9-12 weeks), 59.5 +/- 7.2 pmol g-1 (13-16 weeks) and 117.3 +/- 7.2 pmol g-1 (17-21 weeks). In spina bifida, substance P was severely depleted in the dysraphic segment of the cord (mean concentration +/- S.E.M. = 22.1 +/- 2.3 pmol g-1) and moderately so in the segment above the dysraphism (mean concentration +/- S.E.M. = 47.2 +/- 4.2 pmol g-1).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Maldevelopment of spinal cord--substance P in spina bifida. 242 75

In 30 patients with diagnosed fibromyalgia, the CSF level of immunoreactive substance P (SP) was investigated. Compared to normal values (9.6 +/- 3.2 fmol/ml), all the patients had elevated CSF levels of SP (36.1 +/- 2.7 fmol/ml, range 16.5-79.1 fmol/ml). Anamnestic information from the patients revealed that 53.3% had Raynaud/Raynaud-like phenomenon localized in the fingers, the toes or both. Although SP levels did not differ significantly in patients with or without the Raynaud phenomenon, elevated activity may be present in the peripheral branches of SP neurons which could be responsible for the last (rubor) phase of the triphasic Raynaud's phenomenon. SP levels were significantly higher in patients who were smokers (40.1 +/- 2.7 fmol/ml, range 25.3-64.1 fmol/ml), compared to patients who were non-smokers (29.2 +/- 5.0 fmol/ml, range 16.5-79.1 fmol/ml). We propose elevated CSF levels of SP and the Raynaud phenomenon as characteristic features for fibromyalgia with potential as diagnostic markers of the disease and further that smoking might be an aggravating factor for its pathogenesis or development.
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PMID:Elevated CSF levels of substance P and high incidence of Raynaud phenomenon in patients with fibromyalgia: new features for diagnosis. 244 29

The present study examines the effects of intrathecal administration of selected peptides on nociceptive responses in the rat. Each peptide was delivered via a chronically implanted catheter to the L5 vertebral level. In the tail flick test, VIP (0.65-6.5 nmoles) produced a dose-dependent decrease in reaction time (RT) from 1 to 6-16 min after injection; 6.5 nmoles decreased RT to 37% of control value at 1 min after injection. Galanin (0.65-6.5 nmoles) produced a dose-dependent increase in reaction time at 1 and 6 min; at high doses, many of the rats failed to flick the tail. CGRP (6.5 nmoles) produced a small, transient decrease in RT to 73% of control values at 1 min; 3.25 nmoles were without effect. CSF and 6.5 nmoles of somatostatin, TRH and angiotensin II were without effect. At high doses of galanin and CGRP, rats vocalized to innocuous touch of the tail, as reported for substance P. Von Frey hairs were thus applied to the tail after 6.5 nmoles of VIP, galanin, CGRP or substance P. Vocalization in response to a previously innocuous pressure stimulus was observed at 30 s after injection in all rats given galanin and some rats given CGRP or substance P; the effect lasted 4-8 min. VIP and CSF had no effect. These results suggest that VIP, galanin, CGRP and substance P may act as excitatory agents in nociceptive pathways and that specific peptides may function in the different types of pain modalities; VIP in thermal, galanin in mechanical and substance P and CGRP in both.
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PMID:Effects of intrathecal administration of neuropeptides on a spinal nociceptive reflex in the rat: VIP, galanin, CGRP, TRH, somatostatin and angiotensin II. 245 92

A reversed-phase HPLC system was used to concentrate and separate components of substance P-like immunoreactivity (SP-LI) from human CSF. When CSF was injected and fractions collected, no SP-LI could be detected by radioimmunoassay (RIA) at the retention time of SP or SP-sulfoxide. Instead, SP-LI was detected in later eluting fractions. This SP-LI reacted with two different antisera raised against the C-terminal part of SP, but not with an antiserum against the N-terminal part. A compound with similar properties was also found to be present in neutral extracts of rat dorsal spinal cord. When the late-eluting compound from human CSF was treated with trypsin and rechromatographed on HPLC, an immunoreactive component eluting at the position of SP could be detected with both the C- and N-terminally directed SP antisera. These results suggest that an N-terminally extended form of SP is present in human CSF. Trypsinization also gave two other compounds with affinity for the N- but not the C-terminally directed antisera. This may indicate that N-terminal fragments of SP extended at the N-terminus or SP molecules extended at both the N- and the C-terminus (i.e., preprotachykinins) also are present in human CSF. In 32 CSF samples from depressed patients, SP-LI was determined with a C-terminally directed antiserum with and without prior HPLC separation. SP itself could not be detected, but the late-eluting form of SP-LI could be quantitated in all samples by combined HPLC-RIA. In most samples, there was a relatively good agreement between the SP-LI levels measured with and without HPLC.
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PMID:Detection of N-terminally extended substance P but not of substance P in human cerebrospinal fluid: quantitation with HPLC-radioimmunoassay. 245 10

Immunoreactive substance P was determined in lumbar CSF of 35 healthy volunteers and 60 patients with chronic pain syndromes of at least 6 months duration. No significant relationships were found between substance P levels and age, sex or body height. Substance P levels were lower in chronic pain patients, with either neurogenic (n = 23) or idiopathic pain (n = 37) syndromes, than in the healthy volunteers. Substance P levels were especially low in patients with neurogenic pain with lesions involving the extremities and in those with polyneuropathy, while patients with central pain or pain of the head or face had higher values. Substance P levels were related to depressive symptomatology as determined by means of visual analogue scales and to stable personality traits as determined by means of the Karolinska Scales of Personality (KSP). The most consistent (and inverse) relationship was found between substance P levels and the symptom 'inner tension' and between substance P levels and the personality trait 'psychic anxiety.'
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PMID:Substance P in CSF of patients with chronic pain syndromes. 245 41

Evidence exists to suggest that within the CNS, substance P may be enzymatically cleaved into fragments which may mediate some of the effects of substance P. As we have previously reported on the spinal effects of substance P, the present study examines the effects of selected substance P fragments on reaction time in the tail flick test. Peptides were administered via a chronically implanted intrathecal catheter to the L5 vertebral level in the rat. Administration of 6.5 nmoles of SP(1-7) produced a transient decrease in reaction time at 1 min after injection with a return to above control values by 5 min. Similar administration of SP(7-11) produced a smaller decrease in reaction time at 6 min which lasted until 16 min. Administration of 6.5 nmoles of SP(1-9), SP(8-11) and of CSF were without effect. As the effects of SP(1-7) on reaction time resembled those of similar administration of substance P in the earlier experiments, these results suggest that this fragment may be the active component involved in facilitating the tail flick reflex. Substance P may be degraded to the active fragment prior to receptor activation or alternatively, substance P and SP(1-7) may act on the same receptor.
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PMID:N- and C-terminal fragments of substance P: spinal effects in the rat tail flick test. 245 35

We have measured substance P-like (SPLI) and somatostatin-like (SLI) immunoreactivities in cerebrospinal fluid of 49 patients with peripheral (polyneuropathy, lumboischialgia) and spinal cord disease and in 16 control patients. The patient groups showed significantly higher CSF SPLI levels than controls while the mean SLI levels were unchanged. Fractionated sampling of CSF (total volume 30 ml) in 20 patients with various neurological diseases showed no significant differences between early and late fractions for SLI. In contrast, lumbar-cisternal concentration gradients were negative for SPLI, total protein and IgG, and positive for the dopamine metabolite homovanillic acid and the serotonin metabolite 5-hydroxyindolacetic acid. This suggests that SPLI may be released into the lumbar CSF from lower levels of the neuraxis, presumably the spinal cord and spinal ganglia, whereas SLI stems from diffuse CSF secretion without spinal preponderance.
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PMID:Cerebrospinal fluid immunoreactive substance P and somatostatin in neurological patients with peripheral and spinal cord disease. 246 7

In a study to elucidate molecular mechanisms in pain, substance P-like immunoreactivity (SP-LI) was measured in lumbar CSF from 75 patients with lower back pain. Two samples--one before and one after lidocaine treatment--were obtained from each patient, and total SP-LI was measured in unfractionated (no HPLC) samples. SP-LI data were separated into three categories: placebo responders, pharmacological responders, and pharmacological non-responders. A significant difference was observed between the total SP-LI measurement of first and second samples of pharmacological non-responders. Distribution of SP-LI immunoreactive molecular species in two CSF patient samples (no ODS) was analyzed with a combination of reversed phase (RP) HPLC and RIA. Immunoreactivity in collected HPLC fractions was measured at calibrated retention times of synthetic SP-sulfoxide (SP-O), SP, and SP. Qualitative and quantitative differences in those HPLC-RIA metabolic profiles were observed within and between those two patients' samples. These data indicate that the type and amount of SP metabolism and SP precursor-processing differs in CSF between these two representative patients and within the short amount of time elapsed between acquiring these two samples.
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PMID:Substance P-like immunoreactivity in human cerebrospinal fluid. 247 11

We show that the neuropeptide, substance P (SP), a putative mediator of neurogenic inflammation, is a potent regulator of mature, human neutrophil function. SP increased neutrophil cytotoxic activity against an antibody-coated target (P815 cells) in a dose-dependent manner. The maximal effect was noted at an SP concentration of 10(-4) M, when cytotoxicity increased from 4.7 +/- 0.9% to 33.4 +/- 10.3%. This effect was not due to toxicity of SP against the target cells and was antibody-dependent. The level of cytotoxic activity induced by SP was comparable to that described for a number of cytokines, such as GM-CSF, under identical assay conditions. SP-induced cytotoxicity was 73.1 +/- 5.8% of that produced by an optimum concentration of conditioned medium known to contain a number of cytokines which activate mature neutrophils. In addition, SP enhanced FMLP-stimulated superoxide anion production by neutrophils in a dose-dependent fashion. Neutrophils preincubated with medium or 7.5 x 10(-5) M SP and then stimulated with 10(-7) M FMLP produced 7.9 +/- 2.7 and 29.9 +/- 3.7 nmol superoxide anion/10(6) cells, respectively. This priming effect of SP was rapid in onset (less than 15 min) and was maximal from 15 to 60 min, after which it declined. It was not reversed by washing the cells and was temperature dependent. SP did not shift the dose-response curve to FMLP to the left, but it enhanced the response to FMLP in the concentration range 10(-8)-10(-6) M. Similarly SP enhanced LTB4 and 5-HETE production by FMLP-stimulated but not calcium ionophore-stimulated neutrophils. Therefore, these data provide evidence that SP regulates a number of neutrophil functions and suggests a mechanism whereby the nervous system may affect the immune response. Furthermore, the regulatory effects of SP on the neutrophil functions studied appear to be similar to those of a number of cytokines that have been previously implicated in inflammation.
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PMID:Activation of human neutrophils by substance P: effect on FMLP-stimulated oxidative and arachidonic acid metabolism and on antibody-dependent cell-mediated cytotoxicity. 248 Mar 29

Radioimmunoassays of brain extracts have shown that several peptides occur in high concentrations in the CNS. The releasing-factor peptides TRF, LRF, somatostatin, CRF and GRF have the highest concentration in the hypothalamic extracts. High levels of somatostatin, CCK octapeptide, neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP) are found in cortical extracts. Substance P, CCK, NPY, and enkephalins are present in high concentrations in basal ganglia and mesolimbic areas. Pharmacological doses of these peptides result in several behavioural and vegetative effects. Immunocytochemical studies show that the CNS peptides are localised in neurones and in synaptic vesicles. In vitro studies with brain tissues show that peptides are capable of modifying the ongoing classical neurotransmission. In depressive patients several neuropeptides (CCK, CRF and NPY) have been shown to have low CSF levels. Patients dying of senile dementia have low cortical levels of somatostatin, CRF and substance P. In schizophrenic patients CCK peptides have shown to improve some symptoms. At present the therapeutic potentials of peptides are poorly known. More studies are required to understand their role in neurotransmission and related pathological states.
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PMID:Peptides and neurotransmission in the central nervous system. 282 29


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