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 undecapeptide substance P and the alkaloid morphine sulfate are two agents previously thought to have opposite roles in the mediation of spinal nociceptive processes. The present report, however, demonstrates that low doses of substance P when coadministered with marginally effective doses of morphine sulfate into the rat subarachnoid space produce a markedly enhanced analgesic response, as monitored by the tail-flick test. This pharmacological effect is blocked by prior treatment with the opioid antagonist naloxone, indicating that the potentiated analgesic response is mediated by opioid-responsive neurons. In addition, the putative immediate precursor form of substance P (i.e., substance P-glycine) may substitute for the mature compound in the potentiated pharmacological effect. Moreover, the described synergism is unaffected by transection of the spinal cord, demonstrating the lack of supraspinal modulation of the observed phenomenon. Based on these observations, we are now able to dissociate opioid-potentiating and analgesic properties of substance P from traditional hyperalgesic effects realized at significantly higher concentrations. Consistent with previous biochemical data, a likely mechanism underlying the peptide-mediated enhancement of opioid analgesia may center on the ability of substance P to release endogenous opioid peptides within the local spinal cord environment. Finally, the pharmacological relationship of coadministered substance P and morphine sulfate established here supports the hypothesis that spinal tachykinin and opioid systems have a direct functional interaction in the modulation of local nociceptive responses.
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PMID:Substance P markedly potentiates the antinociceptive effects of morphine sulfate administered at the spinal level. 768 11

Substance P has been previously shown to inhibit the intensity of the morphine abstinence syndrome in mice. In view of the rapid degradation of substance P after its release from nerve terminals, we hypothesized that this inhibition is mediated by the N-terminus of substance P and its metabolites rather than via the C-terminus interacting with neurokinin receptors. Intrathecal injection of substance P-(1-7) (1 nmol) 30 min prior to naloxone challenge, in mice that had received 25 micrograms of morphine sulfate intrathecally once daily for three days, caused a dose-related attenuation of withdrawal jumping. In contrast, administration of the substance P-(1-7) antagonist, [D-Pro2,D-Phe7]substance P-(1-7), 15 min prior to naloxone increased withdrawal jumping behaviors. Equimolar doses of morphine and naloxone at 30 min had no effect. From these data, it appears that substance P N-terminal metabolites modulate withdrawal behaviors in morphine-dependent mice.
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PMID:Substance P-(1-7), a substance P metabolite, inhibits withdrawal jumping in morphine-dependent mice. 769 18

Five commercial fertilizers, Amfos, ammonium sulfate, Kamex, Kieserit and NPK affected the transport of Escherichia coli, Pseudomonas aeruginosa and Salmonella infantis in sand columns. The percentage of cells transported through and without fertilizers during a 2-h period was species-dependent (0.56 for S. infantis, 3.1 for E. coli and 12.4 for P. aeruginosa). The cell transport was enhanced by Kamex for all strains tested, whereas Amfos was found to decrease the transport of E. coli and S. infantis cells. A mathematical model revealed a relationship between the transport of cells and the pH of the sand columns with fertilizers. Columns in which the pH was decreased by the fertilizers exhibited a higher retention of cells. This points to the existence of physico-chemical surface interactions between cells and sand particles.
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PMID:Effect of chemical fertilizers on the transport of Escherichia coli, Pseudomonas aeruginosa and Salmonella infantis through sand columns. 772 64

The nonmammalian tachykinin eledoisin was investigated by use of CD and two-dimensional NMR techniques. In aqueous solution the peptide is conformationally averaged, but on addition of 50% trifluoroethanol (TFE) or sodium dodecyl sulfate (SDS) it adopts an alpha-helical structure. In TFE/H2O and SDS, residues 6-10 of eledoisin show more conformational order than the terminal regions, which undergo dynamic fraying. A possible turn in the N-terminal "address" region, the putative receptor recognition site of the peptide, is detected by NMR spectroscopy but appears to undergo substantial conformational averaging. The NMR data indicate that the helical central core of eledoisin is better defined in the micellar environment than in TFE; however, partial unfolding via 3(10) intermediates occurs in both cases. The conformational preference for SDS-bound eledoisin was examined by three-dimensional structure calculations using NMR-derived distance information in simulated annealing calculations.
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PMID:A determination of the solution conformation of the nonmammalian tachykinin eledoisin by NMR and CD spectroscopy. 820 14

The expression of the alpha 6 beta 4 and alpha 6 beta 1 integrins on epidermal Langerhans cells (LC) before and after mast cell degranulation was studied in cultured human neonatal foreskin by immunohistochemistry. Twenty-four hours after addition of mast cell secretagogues, morphine sulfate, or substance P, solitary mid-epidermal cells showed staining for the integrin subunits alpha 6, beta 4, and beta 1. This expression was not observed in cultured control explants, and immunostained cells were confirmed to be non-epithelial, dendritic cells by immuno-electron microscopy. The identity of these cells as LC was further established by coincident staining for alpha 6 and CD1a using double immunofluorescence labeling. Addition of tumor necrosis factor-alpha (TNF alpha), the predominant cytokine in mast cell granules, also induced LC to express alpha 6 integrins. Furthermore, preincubation of skin organ cultures with anti-TNF alpha antibodies or the mast cell inhibitor cromolyn sodium abrogated the ability to induce alpha 6 integrins on LC consequent to experimental mast cell degranulation by substance P. These data implicate a role for mast cell-derived TNF alpha in the regulation of the integrins alpha 6 beta 4 and alpha 6 beta 1 on LC. These findings may have important implications relevant to mechanisms for spatial localization of LC within the cutaneous compartments during immune responses.
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PMID:Mast cell degranulation upregulates alpha 6 integrins on epidermal Langerhans cells. 834 16

Short chain fatty acids stimulate Cl secretion in rat descending colon in vitro via an enteric reflex involving mucosa and cholinergic nerves. We used the short circuit current as the measure of Cl secretion caused by Na propionate (NaP) (0.5 mM) in luminal bath fluid and studied the mechanism of the response. The NaP response was decreased 81% by atropine and 76% by lidocaine. It was unaffected by tetrodotoxin, omega-conotoxin or by tachyphylaxis to capsaicin, CGRP, substance P, histamine or PGE2. It was not reduced by inhibitors of 5-HT2 or 5HT3 receptors or by partial tachyphylaxis to 5-HT. However, superficial mucosal injury with hypertonic Na sulfate (2 M) or xylose (4.5 M) reduced the NaP response by 90% and 86%, respectively, and mucosal concanavalin A (1 mg/ml) reduced it by 73%. Neither piroxicam (10 microM) nor nordihydroguaretic acid (10 microM) affected the NaP response. We hypothesize that NaP stimulates the superficial epithelium to release an unidentified agonist that depolarizes predominantly cholinergic nerve terminals and causes colonic secretion.
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PMID:Mechanisms of the secretory response to luminal propionate in rat descending colon in vitro. 836 52

The aim of this study was to examine the effects of biglycan, a small chondroitin sulfate proteoglycan with neurotrophic activity, on memory and reinforcement upon unilateral injection into the region of the nucleus basalis magnocellularis (NBM). In experiment 1, rats with chronically implanted cannulas were injected with biglycan and tested on the uphill avoidance task, which involves punishment of a high-probability turning response on a tilted platform (negative geotaxis). Immediately after the training trial, that is, after a tail-shock was administered upon performing the response, rats received one microinjection (0.5 microliter) of substance P (SP) in a reference dosage of 0.74 pmol or biglycan (doses ranging from 1.3 to 1300.0 nmol) into the NBM region. When tested 24 h later, rats treated with SP (0.74 pmol) or biglycan (2.1 and 2.6 nmol) had significantly longer uphill latencies than vehicle (PBS) controls, indicative of superior learning of the avoidance response. In experiment 2, a test for possible proactive effects of post-trial biglycan on performance during the retention trial was performed. Furthermore, the uphill avoidance task was combined with a conditioned place preference task to assess possible reinforcing effects of biglycan. Rats were injected with either 2.6 or 130.0 nmol biglycan immediately after the training trial of the uphill task. One control group received 2.6 nmol biglycan 5 h after the trial, a second group was sham-operated. Additional groups were included which received biglycan (2.6 or 130.0 nmol), SP (0.74 pmol) or PBS after the training trial but no tail-shock.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Facilitation of learning following injection of the chondroitin sulfate proteoglycan biglycan into the vicinity of the nucleus basalis magnocellularis. 851 29

An azido derivative of [3H2](2S, 3S)-cis-2-(diphenylmethyl)-N-((2-methoxyphenyl) methyl)-1-azabicyclo[2.2.2]octon-3-amine (CP-96,345), a potent nonpeptide antagonist of the substance P (SP) (neurokinin-1) receptor, was synthesized and shown to have an affinity for the human SP receptor similar to that of the parent compound, CP-96,345. When Chinese hamster ovary cells expressing the human SP receptor were photolabeled with this compound and analyzed with the use of sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography, several radioactive bands were observed, including a major band centered at molecular mass 80 kDa, the expected value for the SP receptor expressed in Chinese hamster ovary cells. Only the labeling of the 80-kDa protein was specific: nonradiolabeled CP-96,345 but not its optical enantiomer, CP-96,344 was a potent inhibitor of photoincorporation. SP prevented photolabeling only at concentrations higher than expected from its binding affinity but similar to those shown in a competition binding assay to displace radioiodinated analogue of CP-96,345. Antiserum generated against a synthetic peptide corresponding to the carboxyl terminus of the human SP receptor immunoprecipitated only the 80-kDa photoaffinity labeled protein, confirming that it is the human SP receptor. Interestingly, a second antiserum that was generated against the third extracellular loop of the G protein-coupled receptor no longer immunoprecipitated the receptor when covalently labeled with [3H2]azido-CP-96,345. This result indicates either that attachment of the antagonist modified the antigenic region directly, suggesting involvement of this domain in the binding of CP-96,345, or that the loss of recognition by the antiserum is secondary to a change in conformation induced by the covalent attachment of the antagonist at a different site.
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PMID:Photoaffinity labeling of the human substance P (neurokinin-1) receptor with [3H2]azido-CP-96,345, a photoreactive derivative of a nonpeptide antagonist. 862 30

Relatively scant chemical information has been available on the proteinases and peptidases of spirochetes in spite of the association of spirochetes with several serious infections known to plague humans and other animal species. This situation has partly resulted from difficulties in growing some spirochetes under laboratory conditions. The cells of Treponema denticola, a spirochete suggested to be associated with periodontal infections, have turned out to be a good source of new chemical information on those enzymes. Latest studies suggest that the outer cell envelope or the periplasmic space of T. denticola contains several novel proteinases and peptidases (hence called "ectoenzymes") which may contribute to the chronicity of periodontal infections. Some of the oligopeptidases discovered are specific for proline-containing host tissue peptides such as substance P, bradykinin, neurotensin, etc., and possibly small collagen fragments. The only spirochetal peptidases purified to give a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis have been obtained from T. denticola. One particular peptidase, suggested to be similar to the oligopeptidase B (EC 3.4.21.83) of Escherichia coli seems to be present in the cell envelope or in the periplasmic space at quite large concentrations. The presence of this and several other peptidases in the outer cell structures of the treponemes suggests that such enzymes are important for the nutrition of these highly motile and invasive organisms. The biological role of these enzymes can thus be envisaged in the peptidolytic processing of host tissue proteins and peptides to gradually smaller molecules to fulfill the nutritional requirements of these organisms. Although the genetic similarity between T. denticola and some other treponemes and spirochetes can be hotly debated, it is nevertheless now possible to use T. denticula enzymes as suitable objects for comparison when the chemistry of other spirochetes is studied.
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PMID:The peptidolytic capacity of the spirochete system. 880 47

The potent, selective, tachykinin NK1 receptor antagonist, CP-122,721 ([(+)-(2S,3S)-3-(2-methoxy-5-trifluoromethoxybenzyl)amino-2- phenylpiperidine]), at 0.01-1 mg/kg, s.c. reduced retching and vomiting elicited by loperamide, copper sulfate, ipecac syrup and cisplatin in a dose-dependent manner. ID50 values after subcutaneous administration ranged from 0.02 mg/kg (loperamide) to 0.08 mg/kg (ipecac). Oral CP-122,721 reduced cisplatin-induced emesis with an ID50 of approximately 0.08 mg/kg. The less active (2R, 3R)-enantiomer, CP-132.687, did not significantly suppress retching or vomiting induced by any of the emetogens. These data support the hypothesis that CP-122,721 blocks emesis by a specific action at tachykinin NK1 receptors. Its broad spectrum of antiemetic activity suggests a central site of action.
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PMID:Broad spectrum antiemetic effects of CP-122,721, a tachykinin NK1 receptor antagonist, in ferrets. 881 51


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