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 present paper describes histochemical study of the dipeptidylpeptidase IV activity in the nerve structures of cat fungiform papillae at the light and electron microscope levels. The dipeptidylpeptidase IV activity was found in blood vessels and nerve bundles entering the connective tissue stroma of fungiform papillae. The taste buds exhibited a moderate staining for the dipeptidylpeptidase IV activity. Ultracytochemical findings revealed this enzyme as membrane-bound in the endothelium of blood vessels, in plasma membrane of the Schwann cells at the axon-Schwann cell interface as well as in the taste bud cells. A possible function of the dipeptidylpeptidase IV activity in the peripheral nerve structures is discussed in view of the ability of this enzyme to cleave the substance P to the minor fragments with inherent physiological roles.
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PMID:A study of the dipeptidylpeptidase IV activity in cat fungiform papillae: light and electron microscope histochemistry. 290 5

Histochemical investigation by means of light and electron microscopy revealed the presence of dipeptidylpeptidase IV activity in Meissner corpuscles of macaque glabrous skin. The enzyme activity was found in fibroblast-like cells forming an incomplete capsule around the Meissner corpuscle. Distinct electron-dense reaction product due to dipeptidylpeptidase IV activity was consistently localized in the plasma membrane of specialized Schwann cells enveloping the unmyelinated portion of sensory axons. Their axolemma was devoid of dipeptidylpeptidase IV reaction product. The membrane-bound dipeptidylpeptidase IV activity presented here and the occurrence of substance P-containing nerve fibers in primate Meissner corpuscles referred to elsewhere, suggest the possible functional involvement of the enzyme in the production of substance P fragments, influenced in different ways by the axon proper and its surrounding Schwann cells.
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PMID:Dipeptidylpeptidase IV activity in Meissner corpuscles of rhesus monkey and its possible function. 290 70

Active substance P binding sites were solubilized from rat brain membranes by treatment with 0.125% sodium glycodeoxycholate and 1 M NaCl. About 50% of the binding activity in membrane-bound binding sites was recovered in the solubilized fraction after centrifugation at 105,000 g for 1 h. [3H]Substance P absorbed extensively to glass tubes and glass filters, but the absorption was greatly reduced by siliconizing glass tubes and preincubating glass filters in a solution containing poly-D-lysine and bovine serum albumin. [3H]Substance P was found to bind the solubilized receptors in a saturable fashion with a Bmax of 145 fmol/mg protein and a Kd of 4.6 nM, and these bindings were completely replaced by low concentrations of unlabeled substance P and physalaemin.
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PMID:Selective solubilization of physalaemin-type substance P binding sites from rat brain membranes by glycodeoxycholate and NaCl. 301 Nov 90

The electric organ of Torpedo marmorata contains a membrane-bound, captopril-sensitive metallopeptidase that resembles mammalian angiotensin converting enzyme (peptidyl dipeptidase A; EC 3.4.15.1). The Torpedo enzyme has now been purified to apparent homogeneity from electric organ by a procedure involving affinity chromatography using the selective inhibitor lisinopril immobilised to Sepharose via a 28-A spacer arm. The purified protein, like the mammalian enzyme, acted as a peptidyl dipeptidase in cleaving dipeptides from the C-terminus of a variety of peptide substrates, including angiotensin I, bradykinin, [Met5]enkephalin, [Leu5]enkephalin, and the model substrate hippuryl (benzoylglycyl; BzGly)-His-Leu. The hydrolysis of BzGly-His-Leu was activated by Cl-. Enzyme activity was inhibited by classical angiotensin converting enzyme inhibitors, including captopril, enalaprilat (MK422), and lisinopril (MK521). Torpedo angiotensin converting enzyme, like its mammalian counterpart, was also able to act as an endopeptidase in hydrolysing the amidated neuropeptide substance P. Hydrolysis of substance P occurred primarily at the Phe8-Gly9 bond with release of the C-terminal tripeptide, Gly-Leu-MetNH2, and this hydrolysis was blocked by selective inhibitors. The Torpedo enzyme was recognised by a polyclonal antibody to pig kidney angiotensin converting enzyme on immunoelectrophoretic (Western) blot analysis. Thus, on the basis of substrate specificity, inhibitor sensitivity, and immunological criteria, the Torpedo enzyme closely resembles mammalian angiotensin converting enzyme. However, the Torpedo enzyme appears somewhat larger (Mr = 190,000) than the pig kidney enzyme (Mr = 180,000) on sodium dodecyl sulphate-polyacrylamide gel electrophoresis. The endogenous peptide substrate(s) for Torpedo electric organ angiotensin converting enzyme and the physiological role of the enzyme in this tissue remain to be evaluated.
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PMID:Purification and characterization of a peptidyl dipeptidase resembling angiotensin converting enzyme from the electric organ of Torpedo marmorata. 302 62

Water and secretions interact in airways to produce the sol and gel layers that allow for entrapment of foreign materials and subsequent clearance by ciliary movement and by cough. Active Cl ion transport produces fluid, and this process is activated by products of mast cells (leukotrienes), eosinophils (major basic protein), and by other inflammatory mediators (prostaglandins, bradykinin). Gland secretions produce the bulk of the volume of secretions. Airway irritation stimulates gland secretion reflexly via vagal muscarinic pathways. Recently, the sensory nerves have been discovered to release substance P and other neuropeptides when the airways are irritated. The stimulatory effects of neuropeptides on gland secretion (and on other inflammatory sites) are modulated by enkephalinase a membrane-bound enzyme that cleaves neuropeptides and thereby inactivates them. Up- or down-regulation of enkephalinase is predicted to change the degree of inflammatory response to neuropeptides. Finally, the cell surface of airway epithelial cells have been discovered to secrete large molecular weight glycoconjugates; these secreted products are increased markedly by a series of proteinases produced by inflammatory cells (neutrophils, mast cells) and by bacteria. Their exact physiologic roles are still unknown but they may contribute to the bulk and viscoelastic properties of airway secretions, and they may serve an important role in bacterial, viral and inflammatory cell adhesion.
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PMID:Secretion and ion transport in airways during inflammation. 333 78

The effect of inhibitors of the membrane-bound metalloendopeptidase-24.11 ('enkephalinase') on the activity of electrophysiologically identifiable neurons in the substantia nigra is described. Dopaminergic and non-dopaminergic cells were examined. Cells were classified by their responses to striatal stimulation. Only those cells in which the stimulation evoked excitation (alone or mixed with inhibition) responded to the inhibitors. Those cells in which the evoked response was only inhibition did not respond to the drugs. Infusion of 1 mumol of N-[1-(R,S)-carboxy-2-phenyl-ethyl]Phe-pAB (CPAB), 1 or 2 mumol of N-[1-(R,S)-carboxy-3-phenylpropyl]Phe-pAB (CPPAB) into the lateral ventricle produced statistically significant increases (pre- to post-drug treatment) in the spontaneous activity of cells exhibiting excitatory evoked responses: average increases were 33.3%. The increase in spontaneous activity reached an apparent maximum 20 min after the end of the infusion. The increased firing frequency was shown to result from the inhibition of the enzyme, rather than a non-specific effect, as the infusion of 2 mumol of N-[1-(R,S)-carboxy-2-phenyl-ethyl]Leu-pAB, an inhibitor structurally related to CPAB and CPPAB yet two orders of magnitude less potent, was without effect on the activity of nigral neurons. The inhibition of the enzyme by 1 mumol CPAB was verified through in vitro assay. We hypothesize that inhibition of the enzyme enhances peptide-modulated (tachykinin and/or enkephalin) excitation in select neurons of the substantia nigra.
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PMID:Intracerebroventricular infusion of inhibitors of endopeptidase-24.11 ('enkephalinase') increases the spontaneous firing frequency of an identifiable set of cells in the substantia nigra. 348 Aug 7

Vasoactive peptides contain a high proportion of proline residues which make them resistant to hydrolysis by many peptidases. However, post proline cleaving enzyme (PPCE; EC 3.4.21.26), a proline specific endopeptidase which specifically hydrolyzes internal peptide bonds on the carboxyl side of proline residues, has been shown to inactivate numerous vasoactive peptides including angiotensins, kinins, substance P, vasopressin and oxytocin. In order to determine whether PPCE could be involved in vascular metabolism of vasoactive peptides, we carried out localization and characterization studies of PPCE-like activity in hog aorta and mesenteric artery. PPCE was assayed fluorometrically at pH 7.0 using the specific PPCE substrate CBZ-Gly-Pro-4-methyl-coumarinylamide. The subcellular distribution of vascular PPCE was essentially the same as that of the cytosolic marker enzyme lactic dehydrogenase (LDH). PPCE was enriched six-fold in the cytosolic fraction (11.4 +/- 2.7 units/mg) and unlike the plasma membrane-bound proline specific exopeptidase dipeptidyl-(amino)peptidase IV (DAP IV; EC 3.4.14.5), little or no activity could be detected in the microsomal or plasma membrane fractions. Similar to PPCE characterized from other sites, vascular PPCE was stabilized and activated by dithiothreitol and EDTA, and inhibited by DFP, p-chloromercuriphenyl sulfonic acid, L-1-tosylamido-2-phenylethylchloromethyl ketone, Cu++, Ca++, and Zn++. Vascular PPCE was unaffected by inhibitors of trypsin and kallikrein (Aprotinin, ABTI), aminopeptidase M (bestatin, amastatin), neutral endopeptidase (phosphoramidon), angiotensin I converting enzyme (captopril) or carboxypeptidase N (MERGETPA). These data demonstrate that PPCE is present in vascular endothelium and/or smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Vascular, post proline cleaving enzyme: metabolism of vasoactive peptides. 354 18

A neuroendocrine skin carcinoma cell line MKL-1 has been established from a nodal metastasis in a 26-year-old patient. The line grows as irregularly outlined, loosely packed floating aggregates lacking central necrosis. MKL-1 is hyperdiploid and has a mean doubling time of 120 hours. Xenografts of 2 X 10(7) MKL-1 cells produce tumors in nude mice at 4 to 6 weeks after subcutaneous inoculation. The xenografts were morphologically indistinguishable from the original skin primary and the nodal metastasis. Electron microscopy revealed sparse membrane-bound neurosecretory granules, and conspicuous, paranuclear aggregates of intermediate filaments. Immunohistochemical study showed diffuse and consistent staining with neuron-specific enolase, while bombesin, adrenocorticotrophic hormone, Leu-enkephalin, substance P, and vasoactive intestinal polypeptide displayed heterogeneous and variable expression. Uniform staining of all cells appearing as cytoplasmic fibrils and paranuclear aggregates was noted with antibodies to cytokeratin. Appreciable amounts of cytokeratin polypeptides 8, 18, and 19 and IT protein were seen on two-dimensional gel electrophoresis of cytoskeletal preparations from MKL-1 cells and from tumor-rich frozen sections. Immunostaining also showed coexpression of neurofilaments arranged in paranuclear aggregates; gel electrophoresis and immunoblotting demonstrated the presence in MKL-1 cells of prominent amounts of the small neurofilament polypeptide. Focal expression of desmoplakin was noted in the xenografts. The cells reacted with monoclonal antibodies anti-Leu-7 and anti-Leu-M1 but did not react with antibodies to human lymphocyte antigens (HLA)-A, HLA-B, and HLA-C. Cytogenetic analysis revealed the presence of 3 chromosomally abnormal cell lines with the majority of metaphase cells demonstrating a gain of an isochromosome of the short arm of chromosome 5. Thus, MKL-1 cell line shares several characteristics with small cell neuroendocrine bronchopulmonary carcinoma cell lines but shows distinct cytogenetic abnormalities.
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PMID:Establishment and characterization of a neuroendocrine skin carcinoma cell line. 354 33

Rat brain aminopeptidase activity was solubilized from membranes by incubation with thiols. This novel procedure resulted in the release of the same two aminopeptidases (MI and MII) previously shown to be solubilized by the nonionic detergent Triton X-100. The solubilized aminopeptidases MI and MII were resolved by ion-exchange chromatography and further purified by hydroxylapatite chromatography. Aminopeptidase MI was shown to hydrolyze only the beta-naphthylamides of arginine and lysine whereas aminopeptidase MII exhibited a broad specificity with respect to amino acid beta-naphthylamides. Only aminopeptidase MII hydrolyzed Leu-enkephalin at a significant rate, indicating that this enzyme can account for the membrane-bound enkephalin aminopeptidase activity. The enkephalin-degrading aminopeptidase is potently inhibited by opioid (alpha-neo-endorphin and dynorphin) as well as nonopioid (substance P, somatostatin, and angiotensin I) peptides in the range of 0.2-2.0 microM. The regional distribution of aminopeptidases MI and MII in rat brain are rather different, with aminopeptidase MII distribution more closely paralleling the distribution of opiate receptors.
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PMID:Characterization of membrane-bound aminopeptidases from rat brain: identification of the enkephalin-degrading aminopeptidase. 388 43

A membrane-bound 'substance P degrading enzyme' (EC 3.4.24.-) from human brain has been purified to apparent homogeneity. The enzyme was extracted from a membrane fraction of human diencephalon with a non-ionic detergent, Brij 35, and activity was monitored by measuring the rate of disappearance of added substance P using radioimmunoassay, bioassay or radiochemical assay. The enzyme is a thermolabile, neutral metallo-endopeptidase with a relative molecular mass of about 50000. It cleaves substance P between Gln6-Phe7, Phe7-Phe8 and Phe8-Gly9, with a ratio of 0.7:1:1. The breakdown products have been identified by a combination of reverse-phase high-performance liquid chromatography and amino acid analysis. A similar cleavage pattern of substance P has also been demonstrated in a synaptic membrane fraction prepared from rat brain, indicating that a 'substance P-degrading enzyme' is the major peptidase responsible for inactivating the peptide in rat brain membranes. The properties of this enzyme distinguished it from previously described peptidases for which substance P is a substrate. Its high selectivity and its affinity for substance P, among many other neuropeptides, suggest that it may be involved in the physiological inactivation of the peptide by neural tissues.
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PMID:Enzymic inactivation of substance P in the central nervous system. 618 69


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