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)

A membrane-bound metallo-endopeptidase that hydrolyzes human parathyroid hormone (1-84) and reduced hen egg lysozyme between hydrophilic amino acid residues was isolated from rat kidney [Yamaguchi et al. (1991) Eur. J. Biochem. 200, 563-571]. In this study, the hydrolyses of various peptide hormones and neuropeptides by the metallo-endopeptidase were examined using an automated gas-phase protein sequencer. The purified enzyme hydrolyzed the oxidized insulin B chain and substance P most rapidly, followed by big endothelin 1, neurotensin, angiotensin 1, endothelin 1, rat alpha-atrial natriuretic peptide and bradykinin, in this order. The enzyme mainly cleaved these peptides at bonds involving a hydrophilic amino acid residue. However, it cleaved bonds between less hydrophilic amino acid pairs in several short peptides, e.g. at the His5-Leu6 bond in oxidized insulin B chain, the Ile28-Val29 bond in big endothelin-1 and the Ile5-His6 and Phe8-His9 bonds in angiotensin 1. The enzyme cleavage sites of oxidized insulin B chain and angiotensin 1 were different from the reported sites cleaved by meprin and by endopeptidase 2, respectively. Kinetic determination of bradykinin hydrolysis by the purified enzyme yielded values of Km = 18.1 microM and kcat = 0.473 s-1, giving a ratio of kcat/Km = 2.62 x 10(4) s-1.M-1. The Km value was about 20-fold lower than that reported for meprin and endopeptidase 2. These results indicate that the membrane-bound metallo-endopeptidase from rat kidney is distinguished from meprin and endopeptidase 2 in its substrate specificity and is not parathyroid hormone specific, but has potential capacities to inactivate various biologically active peptide hormones and neuropeptides in vivo.
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PMID:A membrane-bound metallo-endopeptidase from rat kidney. Characteristics of its hydrolysis of peptide hormones and neuropeptides. 137 51

1. We have examined the effect of calcitonin gene-related peptide (CGRP) on basal mucus volume, lysozyme and albumin outputs from the ferret whole trachea in vitro, and on the outputs produced by methacholine and substance P (SP). We have also examined the effect of inhibiting neutral enkephalinase with thiorphan on the responses to CGRP. 2. CGRP (1-100 nM) produced small concentration-dependent increases in basal mucus volume, lysozyme and albumin outputs. These effect of CGRP were enhanced by thiorphan. The increases in basal outputs with CGRP and the potentiation by thiorphan were considerably less than previously observed with SP and neurokinin A (NKA). CGRP had no significant effect on potential difference (PD) across the trachea. 3. CGRP produced a concentration-dependent inhibition of methacholine- and SP-induced lysozyme output but a concentration-dependent increase in methacholine- and SP-induced albumin output. The effects of CGRP on methacholine-induced lysozyme and albumin outputs were enhanced by thiorphan. CGRP weakly inhibited methacholine-induced mucus volume output and weakly enhanced SP-induced mucus volume output. 4. Thus, CGRP weakly stimulates basal serous cell secretion and epithelial albumin transport, but does not alter epithelial integrity. CGRP inhibits the serous cell secretion due to methacholine or SP, but potentiates the epithelial albumin transport produced by these agents. The interaction between CGRP and other sensory neuropeptides or muscarinic agonists on airway submucosal glands and epithelium may be important in the normal airway and in inflammatory airway diseases where release of sensory neuropeptides is enhanced.
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PMID:The effects of calcitonin gene-related peptide on submucosal gland secretion and epithelial albumin transport in the ferret trachea in vitro. 171 May 27

To investigate how central and peripheral nerves affect lysozyme secretion from tracheal submucosal glands in ferrets we injected substance P (20 nmol/kg in 200 microliters) intracisternally or intravenously into anesthetized artificially ventilated ferrets. We collected 3-ml samples from a perfused (3 ml/5 min) segment of trachea in situ during 15 min before and 45 min after injection of substance P. Content of lysozyme, a specific marker of tracheal submucosal gland serous cell secretion in ferrets, was measured spectrophotometrically in each sample. Intracisternal substance P increased peak lysozyme output threefold compared with baseline. This increase was abolished completely by cutting both superior laryngeal nerves (SLN) and was partially inhibited by atropine, phentolamine, or propranolol. Intravenous substance P increased peak lysozyme output 10-fold compared with baseline. This increase was partly abolished by cutting both SLN. We concluded that intracisternal substance P stimulated the central nervous system (CNS) and activated cholinergic, adrenergic, and nonadrenergic noncholinergic secretomotor nerves to tracheal glands and that intravenous substance P increased lysozyme secretion both by acting directly on tracheal glands and indirectly on the CNS to activate secretomotor nerves.
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PMID:Neural regulation of lysozyme secretion from tracheal submucosal glands of ferrets in vivo. 172 5

1. The effects of substance P (SP) and neurokinin A (NKA) were examined on tracheal smooth muscle tone, mucus volume output, lysozyme output and albumin transport across the ferret in vitro whole trachea in the presence and absence of the enkephalinase inhibitor, thiorphan. 2. SP (0.001-3 microM) and NKA (0.01-10 microM) contracted the tracheal smooth muscle and increased mucus volume, lysozyme and albumin outputs into the tracheal lumen. The EC50 values for SP and NKA for all of the variables measured were significantly reduced, and all of the maximum responses were significantly enhanced by thiorphan (10 microM). 3. In the presence of thiorphan, SP (1 microM) and NKA (10 microM) produced albumin concentrations in the secreted mucus (8.9 and 7.2 micrograms microliters-1) which were greater than those in the submucosal buffer (4.2 micrograms microliters-1). 4. In the presence of thiorphan, NKA was approximately 5 times more potent than SP at contracting the tracheal smooth muscle. Conversely SP was 23, 15 and 22 times more potent than NKA at stimulating mucus volume, lysozyme and albumin outputs respectively. 5. Thus, there is neutral endopeptidase in the ferret trachea in vitro which cleaves exogenously applied SP and NKA, thereby reducing the magnitude and potency of their actions. SP and NKA contract the ferret tracheal muscle probably by an action at NK2 (or NK3)-receptors but stimulate mucus volume output, lysozyme output and albumin transport across the tracheal wall probably by an action on NK1 receptors.
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PMID:Receptors mediating the effects of substance P and neurokinin A on mucus secretion and smooth muscle tone of the ferret trachea: potentiation by an enkephalinase inhibitor. 248 1

Carcinoid tumors of the middle ear are rare, with only three previously reported cases. The authors report the light and electron microscopic and immunohistochemical features of two carcinoid tumors that occurred in a 34-year-old female and a 21-year-old male. Both presented with unilateral hearing loss. By light microscopic examination, both were characterized by trabecula of tall columnar cells with basal nuclei and no mitotic activity. Electron microscopic examination demonstrated large numbers of pleomorphic neurosecretory granules, perinuclear aggregates of intermediate filaments, cell junctions, and surface microvillous processes. Some cells contained intermediate filaments forming tonofilaments and lacked secretory granules. These cells stained for cytokeratin by immunoperoxidase and separated the neuroendocrine cells from the underlying basal lamina. The cells in this tumor stained for the molluscan cardioexcitatory peptide. Cells in both tumors also stained for pancreatic polypeptide. Neither case stained for lysozyme, insulin, glucagon, somatastatin, gastrin, substance P, thyroid-stimulating hormone, adrenocorticotropic hormone, Met-enkephalin, Leu-enkephalin, neuropeptide Y, peptide YY, neurotensin, Bombesin, serotonin, neuron-specific enolose, glial and neural filaments, S-100 protein, cholecystokinin, beta-endorphin, beta-human chorionic gonadotropin, luteinizing hormone/follicle-stimulating hormone, vasoactive intestinal polypeptide, prolactin or calcitonin. Carcinoid tumor of the middle ear can be distinguished from paraganglioma and middle ear adenoma.
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PMID:Carcinoid tumors of the middle ear. 357 33

Human and canine airway mucosa in vitro synthesizes and secretes mucus glycoprotein, proteoglycans and lipids which can be separated by density gradient ultracentrifugation in caesium bromide. In secretions from unstimulated explants, the small amount of mucus glycoprotein present is found in association with proteoglycans. 'Free' mucus glycoprotein of typical buoyant density is present only after stimulation of submucosal gland secretion by methacholine. Lipids are synthesized, at least in part, by the airway mucosa and occur in explant secretions as a viscoelastic gel, suggesting that they significantly influence the rheological properties of airway mucus. In addition to cholinergic and adrenergic secretomotor neurons, the airway mucosa is innervated by peptidergic fibres containing immunoreactivity to vasoactive intestinal peptide (VIP) and substance P (SP). In explants of non-bronchitic human airway, VIP inhibits baseline glycoprotein and lysozyme secretion; in canine airway mucosa, by contrast, VIP is a weak partial secretory agonist. SP is the most potent agonist of canine airway glycoprotein release described to date and appears to evoke secretion by a direct action on a stereospecific SP receptor rather than by inducing release of other endogenous secretagogues. VIP and SP have little effect on glycoprotein discharge by mucous and serous cells of the submucosal gland; SP appears to induce secretion by causing contraction of submucosal gland ducts. This may represent the most rapid way for delivering mucus into the airway in response to injury or irritation of airway epithelium.
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PMID:Airway mucus: composition and regulation of its secretion by neuropeptides in vitro. 608 50

Goblet-cell carcinoids are particular mucus-producing tumors combining features of typical carcinoids and adenocarcinomas. The immunoreactivity of five goblet-cell carcinoids of the appendix and one tumor of the ileum for 5-hydroxytryptamine (5-HT, serotonin), glucagon, somatostatin, substance P (SP), neuron-specific enolase (NSE), lysozyme, secretory component (SC) and carcino-embryonic antigen (CEA) was compared with that of the mucosa of the appendix (n = 24) and ileum (n = 12), and of typical carcinoids (appendix: n = 10; ileum: n = 3). The goblet-cell carcinoids were consistently lysozyme-, SC- and CEA-reactive and contained weakly NSE reactive endocrine cells, while typical carcinoids were lysozyme-, SC- and CEA-negative, but strongly NSE- reactive. Two goblet-cell carcinoids were glucagon-reactive, one displayed SP-reactivity, one malignant tumor was reactive to the alpha-chain of glycoprotein hormones; six of ten typical appendix carcinoids were SP reactive, as were the three typical ileum carcinoids. Using the immunogold technique combined with the alcian-blue reaction, the presence of 5-hydroxytryptamine (5-HT) and mucus was demonstrated within the same cell. These findings suggest histogenetic differences between goblet-cell carcinoids and typical carcinoids; the former are possibly derived from undifferentiated stem cells, whereas the latter probably arise from endocrine cells in the mucosal stroma.
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PMID:Combined production of mucus, amines and peptides by goblet-cell carcinoids of the appendix and ileum. 648 83

Trigeminal sensory nerves release neurotransmitters such as calcitonin gene-related peptide (CGRP), substance P, and others in human nasal mucosa. The effects of CGRP on nasal secretion were tested in humans in vivo by applying CGRP directly to nasal mucosa and then lavaging the nostrils ten minutes later. Concentrations of total protein, albumin, lysozyme, and orcinol-reactive mucoglycoconjugates were measured in lavage fluid. Calcitonin gene-related peptide (0.1 to 100 micrograms) did not stimulate secretion of any of these markers indicating that CGRP had no effect on glandular secretion or albumin exudation in vivo. These findings indicate that CGRP did not stimulate glands or endothelial cells of the vessels that regulate plasma extravasation. These data are consistent with previous studies that demonstrate 125I-CGRP binding sites on arterial vessels without detecting sites on glands or epithelium, the absence of effects of CGRP on glandular secretion from human nasal mucosal explants in vitro, and the apparently minor magnitude of sensory nerve axon responses in humans in vivo.
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PMID:Calcitonin gene-related peptide nasal provocation in humans. 751 5

We have used the whole cell recording technique to investigate voltage-activated outward currents in cultured ovine trachea submucosal gland cells. The cultured gland cells secreted lysozyme in response to secretagogues, methacholine (20 microM), phenylephrine (100 microM) and substance P (10 microM). Most cells in culture for 7-21 days expressed a voltage-activated outward current at potentials positive to -30 mV. This outward current inactivated slowly, by 44 +/- 6% during a 3 sec depolarization to +30 mV. The voltage-activated outward current was sensitive to the potassium channel inhibitors tetraethylammonium bromide (5 mM), 4-aminopyridine (500 microM) and glibenclamide (1 microM). These data suggest that the outward voltage-activated currents observed are due to K+ channel activity. In cells with little or no outward current present the potassium channel opener Ro 31-6930 produced an additional voltage-activated net outward current. This effect of Ro 31-6930 was sensitive to glibenclamide (1 microM). Our results suggest that some cultured submucosal gland cells express voltage-activated K+ currents with a mixed pharmacology to antagonists and that a portion of this current is sensitive to modulation by Ro 31-6930.
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PMID:Properties of K+ currents recorded from cultured ovine trachea submucosal gland cells. 805 91

Sudden Infant Death Syndrome (SIDS) victims have significantly thickened bronchiolar walls with increased mononuclear cells in the adventitia. An immunohistochemical study was performed on 25 SIDS and 18 aged-matched control infants to characterize these cells. The panel of antibodies included alpha-1-antitrypsin, lysozyme, actin, vimentin, Leu M1, NSE, S-100, Leu 6, bombesin, serotonin, anti-substance P, vasoactive intestinal peptide, MAC 387, and Factor XIIIa. The bronchiolar cells stained with S-100 antibody and demonstrated slender processes similar to dendritic cells, such as Langerhans' cells, and interdigitating reticulum cells, present in normal tissues as well as in certain tumors and inflammatory diseases. Manual counting of the S-100 positive cells and fibers revealed both of these to be significantly increased in SIDS infants as compared to age-matched control infants. Morphologically, the bronchiolar dendritic cells closely resembled Langerhans' cells and therefore may have similar immunologic functions, such as antigen presentation and viral and neoantigen immunosurveillance. We hypothesize that the proliferation of these dendritic cells in SIDS victims is a result of exposure to environmental antigens, resulting in a thickening of the bronchiolar walls, narrowing of the lumen, and reduction in airflow, thus causing a chronic or persistent hypoxia.
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PMID:Proliferation of dendritic cells in the bronchioles of sudden infant death syndrome victims. 834 85


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