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 occurrence and distribution of peptide-containing nerve fibres [substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), neuropeptide Y (NPY)] and noradrenergic nerve fibres [tyrosine hydroxylase (TH)- and dopamine beta hydroxylase (DBH)-positive] in the airways of the pig were studied by means of immunohistochemistry. SP- and CGRP-immunoreactive (-IR) nerve fibres were present close to and within the lining respiratory epithelium, around blood vessels, within the tracheobronchial smooth muscle layer and around local tracheobronchial ganglion cells. The content of CGRP- and neurokinin A (NKA)-like immunoreactivity (-LI) measured by radioimmunoassay (RIA) was twice as high in the trachea compared to that in the peripheral bronchi. SP was a more potent constrictor agent than NKA on pig bronchi in vitro. CGRP had a relaxant effect on precontracted pig bronchi. On blood vessels CGRP exerted a relaxant effect that was more pronounced on pulmonary arteries than on bronchial arteries. VIP/PHI-IR fibres were seen in association with exocrine glands and in the tracheobronchial smooth muscle layer. VIP-positive nerve fibres were abundant around blood vessels in the trachea but sparse or absent around blood vessels in the peripheral bronchi. This histological finding was supported by RIA; it was shown that the content of peptides displaying VIP-like immunoreactivity (-LI) was 18 times higher in the trachea compared to peripheral bronchi. VIP was equally potent as CGRP in relaxing precontracted pig bronchi in vitro. Both bronchial and pulmonary arteries were relaxed by VIP. NPY was colocalized with VIP in tracheal periglandular nerve fibres and in nerve fibres within the tracheobronchial smooth muscle layer. NPY was also present in noradrenergic (DBH-positive) vascular nerve fibres. The content of NPY was much higher (15-fold) in the trachea compared to small bronchi. NPY caused a contraction of both pulmonary and bronchial arteries. The bronchial smooth muscle contraction to field stimulation in vitro was purely cholinergic. A noncholinergic relaxatory effect following field stimulation was observed after bronchial precontraction. Capsaicin had no effect on pig bronchi in vitro.
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PMID:Innervation of lower airways and neuropeptide effects on bronchial and vascular tone in the pig. 169 4

Several lines of evidence suggest a possible role for mast cell proteases in modulating the biologic effects of neuropeptides. To explore the potential of such interactions in human airway, we examined the activity of human tryptase, the major secretory protease of human lung mast cells, against several neuropeptides with proposed regulatory functions in human airway. Using highly purified tryptase obtained from extracts of human lung, we determined the sites and rats of hydrolysis of vasoactive intestinal peptide (VIP), peptide histidine-methionine (PHM), calcitonin gene-related peptide (CGRP), and the tachykinins substance P (SP), neurokinin A (NKA), and neurokinin B (NKB). Tryptase hydrolyzes VIP rapidly at several sites (Arg12, Arg14, Lys20, and Lys21) with an overall kcat/Km of 1.5 x 10(5) M-1 s-1 and hydrolyzes PHM primarily at a single site (Lys20) with a kcat/Km of 1.9 x 10(4) M-1 s-1. Tryptase also rapidly hydrolyzes CGRP at two sites (Arg18 and Lys24) with a kcat/Km of 2.7 x 10(5) M-1 s-1. The tachykinins are not hydrolyzed by tryptase. These observations raise the possibility that tryptase-mediated degradation of the bronchodilators VIP and PHM combined with exaggerated mast cell release of tryptase may contribute to the increase in bronchial responsiveness and the decrease in immunoreactive VIP in airway nerves associated with asthma. The favorable rates of hydrolysis of CGRP suggest that tryptase may also terminate the effects of CGRP on bronchial and vascular smooth muscle tone and permeability.
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PMID:Degradation of airway neuropeptides by human lung tryptase. 169 72

The localization and distribution of seven neuropeptides in the nervous system of the plerocercoid, adult and free proglottis stages of the tetraphyllidean tapeworm Trilocularia acanthiaevulgaris have been determined by an indirect immunofluorescence technique. Six of the peptides are vertebrate-derived, namely, pancreatic polypeptide (PP), peptide tyrosine tyrosine (PYY), vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), substance P (SP) and somatostatin (SRIF); the seventh is the invertebrate neuropeptide, FMR Famide. This is the first demonstration of VIP and SP immunoreactivity in a cestode parasite, and for SRIF this is its first description in any parasitic platyhelminth. Cell bodies and nerve fibres immunoreactive to PP, PYY, VIP, SP and FMRFamide are present throughout the CNS; the distributions of PHI and SRIF were more restricted. In the PNS, nerve fibres immunoreactive to PP occur in the bothridia, whilst in the free proglottis nerve fibres immunoreactive to PYY and VIP innervate the gonads; VIP-immunoreactive nerve elements also supply the reproductive ducts. Extra-neuronal sitings of peptide immunoreactivities were evident for PHI, in association with the excretory system, and for SRIF, in presumed tegumental cell bodies in the free proglottis. The results are discussed in relation to the possible roles of the peptides in the neurophysiology and developmental biology of the worm.
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PMID:Peptidergic nerve elements in three developmental stages of the tetraphyllidean tapeworm Trilocularia acanthiaevulgaris. An immunocytochemical study. 169 77

Immunocytochemical double and triple staining techniques were employed on whole mounts of the submucosal plexus from normal Wistar and non-diabetic BB rat jejunum and ileum, to determine the patterns of co-localization of vasoactive intestinal polypeptide-, peptide histidine-isoleucine-, somatostatin-, neuropeptide Y-, calcitonin gene-related peptide-, substance P-, and galanin-immunoreactive nerves. Neuropeptide Y immunoreactivity was found in 38% of submucosal plexus neurons, within the same neuronal elements as vasoactive intestinal polypeptide immunoreactivity (39% of submucosal plexus neurons) and peptide histidine-isoleucine immunoreactivity. A small population (1% of submucosal plexus neurons) containing vasoactive intestinal polypeptide- and peptide histide isoleucine-like immunoreactivity without NPY-like immunoreactivity was also observed. A significant population of fibers containing vasoactive intestinal polypeptide and galanin immunoreactivity were observed in the mucosa and submucosa, although no cell bodies were detected which contained both neuropeptides. Galanin-like immunoreactivity was seen in a small (2% of submucosal plexus neurons) population, not co-localized with any of the other neuropeptides examined. All somatostatin-immunoreactive neuronal elements (18% of submucosal plexus neurons) contained calcitonin gene-related peptide immunoreactivity, just over half of which also contained substance P immunoreactivity. An additional 25% of submucosal plexus neurons contained calcitonin gene-related peptide- without somatostatin-like immunoreactivity and 28% of submucosal plexus neurons contained substance P without somatostatin-like immunoreactivity. Some degree of co-localization was seen between calcitonin gene-related peptide- and substance P-like immunoreactivity, however, this could not be directly quantified.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The co-localization of neuropeptides in the submucosa of the small intestine of normal Wistar and non-diabetic BB rats. 169 58

Little is known about the influence of cutting the extrinsic pancreatic nerves on the morphology and function of the intrapancreatic nerves in dogs. For this reason, intrapancreatic nerves of mongrel dogs were studied, using electron microscopy and immunohistochemistry, after truncal vagotomy, after celiac and superior mesenteric ganglionectomy, and after a combination of both operations, i.e., removing all extrinsic nerves of the pancreas. Dogs with intact extrinsic and intrinsic pancreatic nerves served as controls. Studies were performed 1-2 weeks and up to 5 months after one or both denervation procedures. For immunohistochemical and electron microscopic studies the animals were perfused with glutaraldehyde-formaldehyde-picric acid solution and the tissue was embedded in Epon or paraffin. Both immunohistochemical and electron microscopic studies revealed that signs of degenerating intrapancreatic nerves occurred only in the early phase (up to 30 days) after operation. After 60 days, hypertrophy of pancreatic nerve fibers was observed. The most striking finding was that the integrity of the intrapancreatic ganglia and nerves was almost preserved after complete extrinsic denervation. In controls there was a strong intrapancreatic innervation with vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine (PHI), substance P (SP), and neuropeptide Y (NPY) nerves. SP and NPY-nerves significantly decreased after the different denervation procedures, but the other peptidergic nerves were not altered by truncal vagotomy, ganglionectomy, or the combination of both procedures. We conclude that the dog pancreas contains extensive intrinsic peptidergic nerves, which, with the exception of SP and NPY-nerves, are greatly independent of the integrity of the extrinsic nerves.
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PMID:Intrinsic pancreatic nerves after mechanical denervation of the extrinsic pancreatic nerves in dogs. 170 29

Many neuropeptides have recently been identified in human and animal airways. These peptides have potent effects on airway caliber, blood vessels, and secretions, raising the possibility that they may be involved in airway diseases such as asthma. Vasoactive intestinal peptide and peptide histidine methionine are potent bronchodilators and may be neurotransmitters of nonadrenergic bronchodilator nerves. In asthma, if these peptides are broken down more rapidly by enzymes from inflammatory cells, this might contribute to exaggerated bronchial responsiveness. Neuropeptides that are found in sensory nerves, such as substance P, neurokinin A, and calcitonin gene-related peptide, have inflammatory effects and might also contribute to the pathology of asthma if released from sensory nerve endings by an axon reflex. These findings may have important therapeutic implications for the future.
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PMID:Neuropeptides and asthma. 170 52

1. Extracts of the liver fluke, Fasciola hepatica from three different hosts (cow, sheep, rat) have been subjected to radioimmunoassay using antisera to 6 mammalian regulatory peptides. 2. Immunoreactivity was measured to pancreatic polypeptide, substance P, peptide histidine isoleucine and gastrin-releasing peptide. Levels of each peptide varied considerably in flukes from different hosts. 3. Reverse-phase HPLC of rat and sheep fluke extracts revealed three molecular forms of tachykinin immunoreactivity and single peaks of pancreatic polypeptide and peptide histidine isoleucine immunoreactivity. No GRP-immunoreactivity was detected by RIA of HPLC fractions.
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PMID:Quantification and partial characterisation of regulatory peptides in the liver fluke, Fasciola hepatica, from different mammalian hosts. 171 29

The levels of 10 regulatory peptides in acid-alcohol extracts of three regions of the small intestine (0-20%, 30-60%, and 70-100%, with respect to distance from the pylorus) have been monitored radioimmunometrically in sham-infected male (6-8 week old) C57 mice and mice given a 5-cysticercoid infection of the rat tapeworm Hymenolepis diminuta and autopsied 10 days postprimary infection and 5 days postsecondary infection (administered 28 days postprimary infection). The regulatory peptides examined were gastrin, gastrin-releasing peptide (GRP), glucagon (= enteroglucagon), motilin, neurotensin (NT), pancreatic polypeptide (PP), peptide histidine isoleucine (PHI), somatostatin (SRIF), substance P (SP), and vasoactive intestinal peptide (VIP). Statistical analyses revealed significant deviations from control values of five of the peptides (enteroglucagon and SP, both elevated; NT, PHI and VIP, all lowered) in intestinal tissue from infected mice; measurement of the same peptides in colonic extracts revealed no significant differences between infected and sham-infected mice. Parallel changes in peptide levels between normal infected and immunosuppressed infected mice were not evident, although elevations in the tissue levels of enteroglucagon and SP were found in infected Wistar rats (normal host). Results are discussed with respect to a peptidergic involvement in the pathology and host immune response to an intestinal tapeworm.
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PMID:Hymenolepis diminuta: changes in the levels of certain intestinal regulatory peptides in infected C57 mice. 171 77

Various peptide immunoreactivities in the respiratory system have been reported, indicating complex physiological mechanisms. There is only little information on the upper respiratory system of man. The present study was carried out to demonstrate regulatory peptides in the nasal mucosa, larynx (vocal cords and ventricular folds) and soft palate of man using highly efficient immunocytochemical methods. In addition, some peptide immunoreactivities were measured by use of radioimmunoassay (RIA). Using indirect immunofluorescence and immunogold-silver staining (IGSS) with silver acetate autometallography, a series of peptides could be detected, including vasoactive intestinal polypeptide (VIP), peptide histidine methionine (PHM), galanin, calcitonin gene-related peptide (CGRP), substance P, neuropeptide tyrosine (NPY), C-flanking peptide of NPY (CPON) and somatostatin. In addition, antibodies to protein gene-product (PGP) 9.5, neuron-specific enolase (NSE), S-100, PHE-5 and neurofilament proteins gave positive reactions in tissue sections. Using RIA, CGRP, substance P, and neurokinin A were measured. Our results demonstrate a complex network of regulatory peptide-containing nerve fibers and the possible existence of endocrine cells regulating various functions of the upper respiratory system, which need to be further investigated.
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PMID:Regulatory peptides and general neuroendocrine markers in human nasal mucosa, soft palate and larynx. 171 32

Since the growth hormone-releasing peptide (GHRP), His-D-Trp-Ala-Trp-D-Phe-Lys-NH2, was found to specifically release growth hormone by a complementary but yet not clearly defined action on the pituitary as well as the hypothalamus, in vitro studies have been performed to demonstrate and characterized GHRP binding sites on peripheral membranes of both the rat anterior pituitary and hypothalamus. Optimum binding assay conditions were established using [125I]Tyr-Ala-GHRP as the radioligand. The membrane binding sites were specific, reversible, saturable and time, temperature, pH and concentration dependent. Computerized analyses of competition experiments suggested two classes of binding sites in both pituitary and hypothalamic membranes. The maximum specific binding was observed at pH 5.0 than the physiological pH in both tissues. Pretreatment of the membranes with trypsin prevented specific binding. The increase in Bmax was statistically significant and showed a 2.0- to 8.9-fold and 5.8- to 11.2-fold in pituitary and hypothalamus, respectively, whereas the affinity constants (Kds) were not significant. Of the synthetic and natural neuropeptides that influence the release of GH from somatotrophs, only (D-Lys3)GHRP, substance P antagonists and growth hormone-releasing factor analog were potent inhibitors of GHRP binding in both tissues.
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PMID:Demonstration and characterization of the specific binding of growth hormone-releasing peptide to rat anterior pituitary and hypothalamic membranes. 171 88


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