UNIPROT:P20366 - FACTA Search

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Query: UNIPROT:P20366 (substance P)
21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acid and neutral proteinases were isolated with the purpose of investigating their participation in the breakdown of hypothalamic peptides and proteins. The acid proteinase was purified about 1000-fold from hypothalamus by precipitation with acetone, chromatography on SP-Sephadex G-50, gel filtration through column of G-100 and chromatography on DEAE-Sephadex A-50. The molecular weight of the enzyme was approximately 50.000. Maximal activity against hemoglobin was obtained at pH 3,2--3,5: serum albumin was split much more slowly. Hypothalamus acid proteinase was partially inhibited by beta-phenyl pyruvate, benzothonium cloride, and was completely inhibited by low concentrations of pepstatin. This proteinase splits somatostatin, Substance P and some C-fragments of Substance P. The probable sites of enzyme action on these peptides were determined by the end group dansyl technique. Neutral proteinase was isolated from the supernatant fraction(100.000 g) of a 0,3 M sucrose homogenate of bovine hypothalamus by chromatography on DEAE Sephadex A-50, gel filtration through Sephadex G-100 and rechromatography on DEAE sephadex A-50 using luliberin as substrate. The rates of breakdown of luliberin and denaturated hemoglobin were measured by fluorometric estimation of acid-soluble peptides wieht o-phthaldialdehyde. The purifed enzyme preparations have a pH optimum of activity at 7--7,5. The enzymes molecular weight was approximatelyy 30--40.000. Enzyme activity was inhibited by L-1-tosylamide-2-phenylethylchloromethyl ketone, p-chloromercuribenzoate and divalent ions Co2+, Zn2+ and was significantly enhanced by dithiothreitol. The Km values for the reaction of hydrolysis of luliberin and hemoglobin were 1,33.10(-5) and 5,2.10(-5) M respectively. The neutral proteinase from the hypothalamus cleaves luliberin, somatostatin and Substance P. Sites of action of the enzyme upon those peptides were determined by means of the dansyl technique. The acid proteinase, most likely cathepsin D, and neutral proteinase from hypothalamus, may play an important role in the formation and breakdown of peptide hormones in the hypothalamus.
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PMID:[Breakdown of luliberin, somatostatin and substance P as an effect of hypothalamic endopeptidases]. 4 63

The differential vulnerability of basal forebrain cells to ibotenate (IBO) or quisqualate (QUIS) was investigated in rats. IBO was also coinjected with cystine (CYS) or zinc (Zn). Cortical choline acetyltransferase (ChAT) and glutamate decarboxylase (GAD) activity, neurotensin receptors, and high-affinity choline uptake sites were quantified in conjunction with radioimmunoassays for neurotensin, substance P, and somatostatin; immunocytochemistry for neurotensin-, somatostatin-, Leu-enkephalin-, and ChAT-positive cells; and in situ hybridization histochemistry of somatostatin, substance P, and enkephalin mRNAs. Compared with the performance of controls, continuous alternation performance in a T maze of IBO+Zn or IBO+CYS rats was better than that of IBO rats, whereas the performance of QUIS rats was unimpaired. Of those neurotransmitter systems examined, only ChAT-immunoreactive cells were vulnerable to IBO or QUIS. However, cholinergic cell loss did not correlate with impaired performance.
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PMID:Basal forebrain neurons and memory: a biochemical, histological, and behavioral study of differential vulnerability to ibotenate and quisqualate. 128 13

Angiotensin converting enzyme (ACE; EC 3.4.15.1) was purified from porcine kidney and lung (endothelial isoenzyme) and testis (testicular isoenzyme) by affinity chromatography on lisinopril-2.8 nm-Sepharose. Atomic-absorption spectroscopy revealed that ACE purified from kidney and lung contained 2.58 and 2.35 atoms of zinc per molecule of enzyme (M(r) 147,000) respectively. In contrast, ACE purified from testis contained only 1.58 atoms of zinc per molecule of enzyme (M(r) 80,000). Thus it would appear that both putative zinc-binding sites in endothelial ACE contain zinc and may therefore be catalytically active. No differences were observed in the pattern of products generated on hydrolysis of benzoyl (Bz)-Gly-His-Leu, substance P, luteinizing-hormone-releasing hormone (LH-RH) and its analogue, des-Gly10-LH-RH-ethylamide, by kidney and testicular ACE. There was also no difference in the initial rates of hydrolysis of Bz-Gly-His-Leu or substance P by the two isoenzymes, although LH-RH and its analogue were hydrolysed twice as rapidly by kidney ACE. It is therefore unlikely that the N-terminal catalytic site in porcine endothelial ACE is predominantly responsible for the atypical cleavage of LH-RH generating the N-terminal tripeptide. Two polyclonal antisera were raised to the affinity-purified forms of pig kidney and testicular ACE. Isoenzyme-specific antisera were then isolated from these by absorbing out those antibodies recognizing determinants on the other isoenzyme. Immunoelectrophoretic blot analyses and immunofluorescent staining of sections of pig kidney were used to demonstrate the specificity of the antisera. Immunofluorescent staining of sections of pig testis with the antiserum specific to testicular ACE localized testicular ACE solely to the lumen of the seminiferous tubules, whereas the antiserum specific to endothelial ACE revealed the presence of this isoenzyme only in blood vessels. The antiserum to endothelial ACE, which recognizes determinants in the unique N-terminal domain, was investigated as a possible specific inhibitor of the N-terminal catalytic site. Although this antiserum failed to inhibit testicular ACE, the effect on the activity of endothelial ACE appeared to be due to inhibition of both the N- and C-terminal catalytic sites.
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PMID:A comparison of the zinc contents and substrate specificities of the endothelial and testicular forms of porcine angiotensin converting enzyme and the preparation of isoenzyme-specific antisera. 133 36

The angiotensin I-converting enzyme (kininase II, ECA) is a membrane bound enzyme anchored to the cell membrane through a single transmembrane domain located near its carboxyterminal extremity. Secretion of ACE by the cell occurs most likely as a result of a posttranslational cleavage of the membrane anchor and intracellular region. The ACE molecule is organized into two large highly homologous domains, each bearing consensus sequences for zinc binding in metallopeptidases. Site directed mutagenesis allowed to establish that both domains bear in fact a functional active site, able to convert angiotensin I into angiotensin II and to hydrolyze bradykinin or substance P. The two active sites of ACE, however, do not display the same sensitivity to anion activation (the C terminal active site being more chloride activatable) and also differs in kinetic parameters for peptide hydrolysis. The C terminal active site can hydrolyze faster angiotensin I and substance P and the N terminal active site is able to perform a peculiar endoproteolytic cleavage of an in vitro substrate of ACE, the luteinizing hormone releasing hormone. Both active sites bind with a high affinity, competitive inhibitors but the Kd of the reaction can vary up to 10 between the two active sites. All together, these observations suggest that ACE contains two active sites, whose structure is not exactly identical. They may have a different substrate specificity, however this remains speculative at the present time. Concerning the regulation of ACE gene expression in man, population studies indicated that the large interindividual variability in plasma ACE levels is genetically determined. An insertion/deletion polymorphism located in an intron of ACE gene is associated with differences in the level of ACE in plasma and cells. The physiological and clinical implications of these observations is discussed.
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PMID:[Angiotensin converting enzyme (kininase II). Molecular and physiological aspects]. 133 89

Neutral endopeptidases EC 3.4.24.11 and EC 3.4.24.15, widely distributed zinc metalloendopeptidases, degrade a number of biologically active peptides including substance P, bradykinin, neurotensin, and luteinizing hormone-releasing hormone. In this study we measured EC 3.4.24.11 and EC 3.4.24.15 activity in alveolar macrophages, key inflammatory cells in the lung that produce and respond to a large number of bioactive substances including chemotactic peptides, with the substrates glutaryl-ala-ala-phe-2-naphthylamide and tertiary butoxycarbonyl-phe-ala-ala-phe-paraaminobenzoate, respectively. We found that specific activity of EC 3.4.24.15, defined as activity inhibited with N-[(1RS)-carboxy-3-phenylpropyl]-ala-ala-phe-paraaminobenzoate+ ++, was significantly higher (p < 0.001) in cells from Sprague-Dawley rats (485 +/- 123 nmol/mg protein.hr) than in cells from Hartley guinea pigs (138 +/- 94 nmol/mg protein.hr), healthy human male smokers (121 +/- 73 nmol/mg protein.hr) and healthy human male nonsmokers (94 +/- 12). In contrast, activity of EC 3.4.24.11, defined as activity inhibited with N-[(1RS)-carboxy-3-phenylpropyl]-phe-paraaminobenzoate, was significantly higher (p < 0.001) in cells from human smokers (689 +/- 167 nmol/mg protein.hr) and nonsmokers (762 +/- 136 nmol/mg protein.hr) than in cells from rats (52 +/- 12 nmol/mg protein.hr) and guinea pigs (34 +/- 14 nmol/mg protein.hr). An additional activity in alveolar macrophages toward tertiary butorycarbonyl-phe-ala-ala-phe-paraaminobenzoate was inhibited with L-3-carboxy-trans-2,3-epoxypropionyl-leucylamido-(4-guanido) butane, a specific inhibitor of cysteine proteinases, a finding of interest because in general enzymes in this class show little activity at neutral pH.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Identification of two zinc metalloendopeptidases in alveolar macrophages of rats, guinea pigs, and human beings. 140 35

The distribution of zinc in the diencephalon of the rainbow trout, Oncorhynchos myciss, is described in the present paper, which is the second in a series of three reporting for the first time the distribution of a heavy metal in the fish brain. The Neo-Timm method was used for the histochemical demonstration of zinc. The staining was essentially confined to the neuropil, in all probability representing stained axon terminals, but stained nerve cell bodies were observed in the nucleus lateralis geniculatus and the nucleus cerebellosus hypothalami. Stained fibers were never seen. The staining gave rise to a consistent, specific distribution pattern, which accorded well with the diencephalic nuclei defined on the basis of cytoarchitectural criteria. The diencephalon was in general stained with much higher intensity than the telencephalon, in surprising contrast to the state of affairs in the mammalian, reptilian, and avian brain. In species of these classes, high staining intensities are observed almost exclusively in the telencephalon. The Neo-Timm staining was predominantly distributed in the nuclei of the periventricular zone, but some internal (migrated) nuclei did show a positive staining reaction, namely the nucleus lateralis geniculatus, the anterior thalamic nucleus, the nucleus diffusus tori lateralis, and the nucleus cerebellosus hypothalami. The zinc distribution pattern has been compared with the terminal fields of afferent projections, known from experimental studies, and with the distribution of substance P. The possible function of zinc in synaptic vesicles is considered.
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PMID:Histochemical distribution of zinc in the brain of the rainbow trout, Oncorhynchos myciss. II. The diencephalon. 141 77

The present paper which describes the distribution of zinc in the telencephalon of the rainbow trout, Oncorhynchos myciss, is the first report on the distribution of a heavy metal in the fish brain. Zinc was demonstrated histochemically by silver enhancement using the Neo-Timm method. The staining was mainly confined to the neuropil, but both moderately and intensely stained nerve cell bodies were of common occurrence. Stained fibers were never observed. The staining revealed a specific distribution pattern which could easily be correlated with the telencephalic nuclei defined on the basis of cytoarchitectural features. However, the telencephalon stained much more weakly than the rest of the brain, in striking contrast to the situation in the reptilian, mammalian, and avian brain. In these classes, high staining intensities are observed almost exclusively in the telencephalon. The staining was essentially restricted to the nuclei of the ventral telencephalic area. In the dorsal telencephalic area, only the medial and central zones and medial part of the posterior zone showed comparable staining intensities. The Neo-Timm staining pattern lends support to the view that the pallio-subpallial boundary is between the medial and dorsal zones of the dorsal telencephalic area. The distribution of zinc has been compared with the terminal field of afferent projections, known from experimental mapping, and also with the distribution of substance P and vasoactive intestinal peptide. Finally, the possible functional implications of zinc in synaptic vesicles are considered.
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PMID:Histochemical distribution of zinc in the brain of the rainbow trout, Oncorhynchos myciss. I. The telencephalon. 160 64

A distinct subdivision of the striatum has recently been described which is located at the caudomedial margin of the striatum, surrounding the rostrolateral edge of the globus pallidus. This "marginal division" has an internal organization and an efferent distribution which is distinct from the rest of the striatum. The striatum contains moderately high levels of zinc and the neuropeptides enkephalin, dynorphin and substance P. In the present study we have examined the distribution of histologically detectable zinc and of dynorphin B- and substance P-immunoreactivity in the marginal division of the striatum. Each of these substances was more dense within the confines of the marginal division than in the rest of the striatum. These data provide further evidence that the marginal division is a structurally distinct subdivision of the striatum.
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PMID:High density of zinc-containing and dynorphin B- and substance P-immunoreactive terminals in the marginal division of the rat striatum. 169 Oct 46

The effects of zinc gluconate have been studied on rat peritoneal mast cells and rat basophilic leukemia cells (RBL 2H3) stimulated by various secretagogues. The IC50's of zinc gluconate on peritoneal cells were (microM): 1.6, 1.9, 5.4 and 18 for ionophore A23187, phorbol 12-myristate 13-acetate, substance P and immunoglobulin E-antigen, respectively. Higher concentrations of zinc gluconate were required to inhibit histamine secretion from RBL 2H3 cells, i.e. 12 microM (ionophore A23187) and 140 microM (immunoglobulin E-antigen). Zinc gluconate (10(-4) to 10(-3) M) also inhibited the IgE-dependent contraction of guinea pig trachea but was unable to affect that induced by exogenous histamine. These results suggest that zinc gluconate acts intracellularly and is selective of "typical" or "connective tissue" mast cells.
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PMID:The sensitivity to Zn2+ discriminates between typical and atypical mast cells. 169 23

Schistosomiasis mansoni is a parasitic disease in which granulomas form around schistosome eggs in the liver and intestines. The purpose of this study was to determine the alterations in the intrinsic innervation of the distal ileum and proximal colon resulting from schistosomiasis. Using murine schistosomiasis mansoni, we examined light microscopic preparations stained with osmium-zinc iodide or the dihydronicotinamide adenine dinucleotide: nitro BT oxidoreductase (NADH) method. We also examined specific populations of peptidergic nerves (vasoactive intestinal polypeptide and substance P) using an avidin-biotin complex (ABC) immunohistochemical technique. We found that granulomas focally destroyed the enteric nerves. Occasionally nerves were found within granulomas, particularly at the periphery of the lesions. Nerve cell bodies close to granulomas had altered staining, which included increased staining for vasoactive intestinal polypeptide. The distribution of nerve injury varied between the 2 enteric segments studied. In the distal ileum, the principal injury was to the myenteric plexus; whereas, the submucous and mucosal plexuses were predominantly damaged in the proximal colon. The physiologic significance of this injury to the enteric nerves requires elucidation.
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PMID:Alterations of the intestinal innervation in mice infected with Schistosoma mansoni. 171 Feb 71

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