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)

Authors have often experienced that psychological stress influences rheumatoid arthritis (RA). In addition, recent reports show a modulatory role for neuropeptide such as substance P in arthritis. These findings prompted us to study endogenous opioid peptides in RA, which are found mainly in the brain and have an effect on the central nervous system. We examined methionine-enkephalin (Met-enk), leucine-enkephalin (Leu-enk) and beta-endorphin (beta-end) in opioid peptides. We measured these peptides in plasma and synovial fluid samples obtained from 28 knees of 24 RA patients and the quantity in the synovial tissue of 13 knees. We also measured plasma and synovial fluid samples from patients with osteoarthritis of the knee and plasma samples from healthy candidates. Leu-enk and beta-end levels in synovial fluid were significantly higher than plasma levels only in RA. Larger quantity of Leu-end and beta-end were contained apparently in the synovial tissue than Met-enk. The synovial tissue with proliferative change tends to contain larger quantity of opioid peptides. These results indicate that the synovial tissue produces or secretes Leu-enk and beta-end and that opioid peptides are related to the degree of inflammation in RA.
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PMID:[A study of opioid peptides in synovial fluid and synovial tissue in patients with rheumatoid arthritis]. 152 70

The Wobbler mouse possesses an inherited form of motoneuron disease that expresses itself most dramatically in the forelimbs. Previous immunocytochemical (ICC) studies have shown that neuronal processes containing substance P (SP), thyrotropin releasing hormone (TRH) and serotonin (5-HT) seem to sprout in the ventral horn of the cervical spinal cord taken from the Wobbler mouse. By radioimmunoassay, increased concentrations of spinal SP, TRH, and 5-HT, as well as leucine and methionine enkephalins (LE, ME) have been documented. The present ICC study quantifies the numbers of neuronal processes in the Wobbler cervical spinal cord and brainstem which contain SP, 5-HT, LE, ME and other neuropeptides (cholecystokinin, CCK; neuropeptide Y; galanin; calcitonin gene-related peptide, CGRP). It is proposed that those processes that sprout early in the mononeuron disease (5-HT, LE, ME, CCK and also TRH according to other studies) may be involved in the etiology. In addition, it is hypothesized that the loss of CGRP within the ventral horn may represent the loss of a trophic factor that is important to the survival motoneurons and may influence the increase of fiber densities around the dying motoneurons.
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PMID:Decreased immunoreactive (IR) calcitonin gene-related peptide correlates with sprouting of IR-peptidergic and serotonergic neuronal processes in spinal cord and brain nuclei from the Wobbler mouse during motoneuron disease. 152 46

A novel metallo-endopeptidase from human neuroblastoma NB-OK-1 cells was partially purified and characterized. This enzyme activity was detected in the culture medium and could be detached from intact cells by gentle washing, suggesting a peripheral localization of the enzyme. This endopeptidase inactivated Atrial Natriuretic Peptide (ANP) by a unique and selective cleavage of the Ser123-Phe124 bond. It also produced hydrolysis at the Xaa-Phe, Xaa-Leu, or Xaa-Ile bonds of other peptide hormones such as bradykinin, somatostatin 14, litorin, substance P, neuromedin C and angiotensin II. The substrate selectivity and inhibition profile of the enzyme showed obvious similarities with the peptide hormone inactivating endopeptidase (PHIE) recently purified from Xenopus laevis skin secretions and indicated a thermolysin-like activity distinct from neutral endopeptidase (EC 3.4.24.11) and from angiotensin converting enzyme (EC 3.4.15.1).
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PMID:A new metallo- endopeptidase from human neuroblastoma NB-OK-1 cells which inactivates atrial natriuretic peptide by selective cleavage at the Ser123-Phe124 bond. 153 Oct 11

The topographical distribution of neuropeptide-containing cell bodies, fibers and terminals was studied in human parabrachial nuclei and the pontine tegmentum with immunohistochemical stainings. Brains of seven adult human subjects of 35-72 years were fixed within 2 h post mortem. Serial sections were immunostained by antisera of 14 different neuropeptides--oxytocin, vasopressin, thyrotropin-releasing hormone, angiotensin II, calcitonin gene-related peptide, beta-endorphin, dynorphin A, dynorphin B, leucine-enkephalin, alpha-melanocyte stimulating hormone, substance P, neuropeptide Y, cholecystokinin and galanin--alternately. All of these peptides were found to be present in nerve fibers and terminals, but only two, angiotensin II and dynorphin B, in cell bodies of the parabrachial nuclei. Calcitonin gene-related peptide-, neuropeptide Y-, cholecystokinin- and galanin-immunoreactive cells were present in other areas of the pontine tegmentum, like the motor trigeminal nucleus, locus coeruleus, periventricular gray matter but not in the parabrachial nuclei. Peptidergic fibers were distributed unevenly throughout the pontine tegmentum having unique, individual distribution patterns. In the parabrachial nuclei, substance P, neuropeptide Y, cholecystokinin and galanin showed the highest density of immunoreactive neuronal networks. Moderate to low concentrations of immunoreactive processes were detected by calcitonin gene-related peptide, alpha-melanocyte stimulating hormone, dynorphin B, thyrotropin releasing hormone, leucine-enkephalin, dynorphin A, angiotensin II, beta-endorphin, vasopressin and oxytocin antisera, respectively. Other pontine tegmental areas, like the locus coeruleus, dorsal tegmental, pontine raphe and motor trigeminal nuclei as well as the central gray of the tegmental region exhibited a varying assortment of neuropeptides with distinct, individual localization patterns. Their detailed topographical distributions are mapped and given in coronal sections.
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PMID:Immunohistochemical study on the distribution of neuropeptides within the pontine tegmentum--particularly the parabrachial nuclei and the locus coeruleus of the human brain. 154 21

Recent studies have shown that neuropeptides, such as substance P, are responsible for arthritis. We therefore studied opioid peptides (beta-endorphin, Methionine-enkephalin, Leucine-enkephalin) in order to confirm our belief that mental status may have some influence on the activity of rheumatoid arthritis (RA). We examined opioid peptides, lymphocyte subsets, psycologic test (Cornell Medical Index-Health questionnaire (CMI), the Face scale) and clinical data in patients with RA. Plasma Leu-enk, % Leu2a+ Leu15- cells,% Leu3a+ Leu8- cells and % Leu11+ Leu7- cells were higher in patients with a larger number of psycologic complaints in CMI. Plasma Leu-enk concentration was higher while % Leu11+ Leu7- cells was lower in proportion to the degree of neurosis, as indicated by the descrimitive chart of CMI. Plasma Met-enk concentration, % Leu2a+ Leu15- cells, and Lansbury's index were significantly higher in the group of patients whose facial expression was more severe. These findings suggest that mentala status have some relationship with the plasma level of opioid peptides (enkephalins) and immunologic functions, and that it may exert indirect effects on RA.
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PMID:[Psychosomatic medicine in rheumatoid arthritis]. 158 48

A comprehensive high-performance liquid chromatographic, radioimmunoassay, and enzymatic degradation scheme has been developed to analyze several intact neuropeptides and the corresponding peptides created by in vivo enzymolysis of precursors to study neuropeptides in human lumbar cerebrospinal fluid (CSF) and to test the hypothesis that defects in the metabolism (synthesis, degradation) of neuropeptide precursors, neuropeptides, and metabolites play a role in low back pain. CSF samples were obtained from three different patient groups: controls (C), whose low back pain was relieved without lidocaine; pharmacological responders (PR), whose pain was relieved by lidocaine and who were candidates for surgery; and pharmacological non-responders (PNR), whose pain was not relieved by lidocaine and a mid-thoracic anesthetic, and who were not candidates for surgery. The metabolic activity involved during synthesis and degradation of the peptides was assessed by measuring intact, native neuropeptide immunoreactivity in pre-incubated and post-incubated CSF samples, where samples were incubated at 37 degrees C for 1 h. Pre-incubation radioimmunoassay measurements reflected the content of intact peptides present in lumbar CSF at the time of sampling, and post-incubation measurements assayed the amount of peptide that had remained embedded within its precursors [cryptic methionine enkephalin (ME)] and that had been released by the action of CSF peptidases. Significant differences were found in post-incubation samples for the amount of proenkephalin A [ME, leucine enkephalin (LE)] and tachykinin [substance P (SP)] peptides. For example, significant differences were observed for ME-like immunoreactivity (C versus cryptic), SP-like immunoreactivity (PNR versus PR), and LE-like immunoreactivity (PR versus C). No significant differences were observed among the peptides within the pre-incubation samples.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Analysis of proenkephalin A, proopiomelanocortin and protachykinin neuropeptides in human lumbar cerebrospinal fluid by reversed-phase high-performance liquid chromatography, radioimmunoassay and enzymolysis. 162 97

Chromaffin granules, the secretory organelles of the neuron-like adrenal medullary chromaffin cells, have previously been shown to store and liberate neurotrophic activities that support in vitro survival of several neuron populations including those innervating the adrenal medulla. Molecules resembling fibroblast growth factor and ciliary neurotrophic factor have been identified among these activities. Since chromaffin granules store a variety of neuropeptides and many neuropeptides can have pleiotropic effects on neuronal growth and maintenance we have tested 24 different neuropeptides for their capacities to promote survival of embryonic chick ciliary, dorsal root and sympathetic ganglionic neurons. Peptides tested included several derivatives of proenkephalin (Leu- and met-enkephalin, fragments BAM 22, B, F and E), somatostatin, substance P, neuropeptide Y, neurotensin, VIP, bombesin, secretin, pancreastatin, dynorphin B, dynorphin 1-13, beta-endorphin, alpha-, beta-, and gamma-MSH. Control cultures received saturating concentrations of ciliary neurotrophic or nerve growth factor (CNTF; NGF), or no trophic supplements. At 1 x 10(-5) M leu- and met-enkephalin as well as somatostatin supported sympathetic neurons to the same extent as NGF. At the same concentrations, leu-enkephalin, the proenkephalin fragments BAM 22 and E, and somatostatin maintained about half of the dorsal root ganglionic neurons supported by NGF, but were not effective on ciliary neurons. VIP promoted the survival of approximately 50% of the ciliary and embryonic day 10 dorsal root ganglionic neurons as compared to saturating amounts of CNTF, but required the presence of non-neuronal cells in the cultures to be effective. Neurotensin (1 x 10(-5) M had a small effect on ciliary neurons.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Screening of adrenal medullary neuropeptides for putative neurotrophic effects. 163 76

1. The classification of tachykinin receptors in the guinea-pig trachea has been investigated. This was of interest because, from previous studies, it was not clear whether the guinea-pig trachea contains either a mixture of NK1 and NK2 receptors or, alternatively, a single type of novel tachykinin receptor. 2. In the present study, the guinea-pig trachea was contracted by tachykinin agonists selective for NK1 receptors (substance P methylester (SPOMe) and GR73632) or NK2 receptors (GR64349) but not NK3 receptors (senktide). 3. Against SPOMe and GR73632, the NK1 antagonist, GR71251, behaved as a reversible competitive antagonist having apparent affinity (pKB 7.05 vs SPOMe) consistent with action at NK1 receptors. GR71251 (3 microM) did not antagonize responses to GR64349. 4. The NK2 antagonists L-659,877 and Ac-Leu-Asp-Gln-Trp-Phe-Gly-NH2 (R396) antagonized GR64349 although only R396 appeared to behave competitively (pKB 5.73). Neither L-659,877 (30 microM) nor R396 (30 microM) blocked responses to SPOMe. 5. For L-659,877 and R396, comparison was made between activity in guinea-pig trachea and in preparations known to contain tachykinin receptors predominantly of the NK2 type. In the rabbit trachea, both L-659,877 and R396 had effects similar to those in guinea-pig trachea. In contrast, in the rat colon muscularis mucosae, both L-659,877 and R396 appeared to behave competitively with pKB values against GR64349 of 7.83 and 6.90 respectively. 6. It is concluded that in guinea-pig trachea, contractile responses can be induced by activation of both NK1 and NK2 receptors. The present data are discussed with reference to the proposed existence of subtypes of the NK2 receptor.
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PMID:Receptors mediating tachykinin-induced contractile responses in guinea-pig trachea. 165 74

Several N-carboxyalkyl peptides were synthesized and tested as inhibitors of pig synovial collagenase, 72-kDa gelatinase and stromelysin (matrix metalloproteinases MMP-1, MMP-2, and MMP-3). The most potent of the series, CH3CH2CH2(R,S)CH(COOH)-NH-Leu-Phe-Ala-NH2, competitively inhibited cleavage of dinitrophenyl-Pro-Leu-Gly-Leu-Trp-Ala-D-Arg-NH2 at the Gly-Leu bond by MMP-1 and MMP-2 (KI = 30 and 40 microM, respectively). A similar inhibitory potency was found for MMP-1 with soluble Type I collagen and MMP-3 with substance P as substrate. The inhibitor was coupled to EAH-Sepharose 4B through a C-terminal amide. In the presence of 2 M NaCl at pH 7.2, this matrix bound MMP-1, MMP-2, and MMP-3 from concentrated culture medium of pig synovial membranes. The enzymes coeluted at pH 4.1 and subsequently were resolved by chromatography on DEAE-Sephacel and heparin-Sepharose. Purified MMP-1 catalyzed the o-phenanthroline-sensitive cleavage of collagen into TCA and TCB fragments as well as slower hydrolysis of the alpha 2 chain. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of MMP-1 indicated a predominant polypeptide of approximately 44 kDa and minor species of approximately 24 and 21 kDa. The 44-kDa species and one of the smaller polypeptides reacted with an antiserum to residues 195-207 of human fibroblast MMP-1, indicating that porcine MMP-1 contains a similar sequence and that the smaller components were probably derived from MMP-1. Neither MMP-2 nor MMP-3 reacted with this antiserum. Purified porcine MMP-2 degraded gelatin but not collagen and exhibited an apparent Mr of approximately 71 kDa. Additional smaller polypeptides were present, one of which may correspond to tissue inhibitor of metalloproteinases. MMP-3 showed doublets of approximately 47/46 and 26/25 kDa and cleaved substance P at the Gly6-Phe7 bond. This procedure provides a rapid means of obtaining all three MMPs from one source in approximately 15% yield each.
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PMID:Application of N-carboxyalkyl peptides to the inhibition and affinity purification of the porcine matrix metalloproteinases collagenase, gelatinase, and stromelysin. 165 8

NKA (4-10), the C-terminal heptapeptide fragment (Asp-Ser-Phe-Val-Gly-Leu-Met-NH2) of tachykinin NKA, is more active than the parent native compound in the interaction with the NK-2 receptor. Substitution of Gly8 with the more flexible residue beta-Ala8 increases its selectivity with respect to other two known receptors (NK-1 and NK-3), whereas substitution with either D-Ala8 or GABA8 deprives the peptide of its biological activity. These findings can be interpreted by a conformational analysis based on NMR studies in DMSO-d6 and in a DMSO-d6/H2O cryoprotective mixture combined with internal energy calculations. NKA(4-10) is characterized by a structure containing a type I beta-turn extending from Ser5 to Gly8, followed by a gamma-turn centered on Gly8, whereas for [beta-Ala8]NKA(4-10) is possible to suggest a type I beta-turn extending from Ser5 to beta-Ala8, followed by a C8 turn comprising beta-Ala8 and Leu9 and by another beta-turn extending from beta-Ala8 to the terminal NH2. The preferred conformation of [beta-Ala8]NKA(4-10) is not compatible with models for NK-1 and NK-3 agonists proposed on the basis of rigid peptide agonists [Levian-Teitelbaum et al. (1989) Biopolymers 28, 51-64; Sumner & Ferretti (1989) FEBS Lett. 253, 117-120]. The preferred solution conformation of [beta-Ala8]NKA(4-10) may thus be considered as a likely bioactive conformation for NK-2 selective peptides.
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PMID:Conformation-activity relationship of tachykinin neurokinin A (4-10) and of some [Xaa8] analogues. 165 41


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