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 role of neuropeptides in the regulation of macromolecule secretion from human nasal mucosa is incompletely understood. Previous in vitro explant culture studies have demonstrated the effects of neuropeptides on lactoferrin release from serous cells and 3H-glucosamine labeled respiratory glycoconjugate secretion from mucus-containing cells. The generation of a new monoclonal antibody, 7F10, has led to the development of an ELISA for high molecular weight respiratory mucous glycoproteins (MGP). This ELISA was used to measure the ability of sensory, parasympathetic and sympathetic neuropeptides to stimulate MGP release from human nasal mucosal fragments in short term explant culture in vitro. Significant MGP release was stimulated by the sensory neuropeptides gastrin releasing peptide (10 microM GRP: 10.6% +/- 2.4% increase, n = 8, P less than 0.01 vs. control), substance P (1 microM SP: 12.5% +/- 5.4%, n = 11, P less than 0.05), neurokinin A (1 microM NKA: 17.8 +/- 4.3%, n = 6, P less than 0.01), while calcitonin gene related peptide (CGRP) was without effect. Vasoactive intestinal peptide (VIP), a neurotransmitter from parasympathetic nerves, induced significant dose dependent MGP secretion, but had no additive or inhibitory interaction with methacholine-induced secretion. Neuropeptide Y (NPY), present in sympathetic nerves, had no effect on MGP secretion. These observations correlate with the effects of neuropeptides on serous cell lactoferrin secretion, and the presence of specific GRP, SP, and VIP binding sites on human nasal submucosal glands that have been detected by autoradiography. GRP and tachykinins (SP and NKA) from sensory nerves, and VIP released during parasympathetic reflexes may significantly stimulate mucous and serous cell secretion from human nasal mucosa in vivo.
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PMID:The effects of neuropeptides on mucous glycoprotein secretion from human nasal mucosa in vitro. 138 97

Autonomic dysfunction is an increasingly recognized problem in aging animals and man. The pathologic changes that produce autonomic dysfunction in human aging are largely unknown; however, in experimental animal models specific pathologic changes have been found in selected sympathetic ganglia. To address whether similar neuropathologic changes occur in aging humans, the authors have examined paravertebral and prevertebral sympathetic ganglia from a series of 56 adult autopsied nondiabetic patients. They found significant, specific, age-related neuropathologic lesions in the prevertebral sympathetic superior mesenteric ganglia of autopsied patients. Markedly swollen dystrophic preterminal axons compressed or displaced the perikarya of principal sympathetic neurons. Ultrastructurally, these swollen presynaptic axons contained abundant disoriented neurofilaments surrounded by peripherally marginated dense core vesicles. Immunohistochemical studies demonstrated that dystrophic axons contained tyrosine hydroxylase and neuropeptide tyrosine (NPY)-like immunoreactivity but not other neuropeptides (VIP, substance P, gastrin-releasing peptide [GRP]/bombesin, met-enkephalin). Similar to the animal models of aging, lesions were much more frequent in the prevertebral superior mesenteric ganglia than in the paravertebral superior cervical ganglia. These studies demonstrate anatomic, peptidergic, and pathologic specificity in the aging human nervous system similar in many respects to that which the authors have described in experimental animal models. Neuroaxonal dystrophy in the sympathetic nervous system may underlie poorly understood alterations in clinical autonomic nervous system function that develop with age.
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PMID:Neuroaxonal dystrophy in aging human sympathetic ganglia. 169 57

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

We have found vasoactive intestinal polypeptide (VIP)-, neurotensin-, substance P-, gastrin-releasing peptide-, calcitonin-, calcitonin gene related peptide (CGRP-2)-, and somatostatin-like immunoreactivities in extracts of sporadic human parathyroid adenomas (n = 18). The content of CGRP-2, substance P, and somatostatin in adenomas correlated directly with that of parathyroid hormone. In addition, concentrations of VIP versus substance P and somatostatin versus CGRP-2 in adenomas were directly correlated. Neuropeptide content of parathyroid hyperplasias differed from that of adenomas. VIP was detected in only one of seven parathyroid hyperplasias, and neurotensin was undetectable (0/7), whereas substance P was present in six of seven cases and GRP in five of seven hyperplasias. In hyperplasias, content of substance P correlated directly with that of gastrin-releasing peptide. Peroxidase immunohistochemistry localized VIP-like immunoreactivity to 20% to 50% of both chief and oxyphilic cells and rare clear cells and capillary endothelium in 11 of 12 adenomas studied. Focal staining was present in glandular epithelium of the rim of adjacent normal parathyroid tissue and in two of three normal parathyroid glands removed with thyroid goiters. This staining was both cytoplasmic and apical membrane. By contrast, in adenomas, neurotensin- and substance P-like positivities were confined to scattered (5% to 10%) oxyphilic cells. Cytoplasmic positivity for parathyroid hormone, noted in 30% to 70% of cells in serial sections, confirmed that these tissues were indeed parathyroid glands.
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PMID:Vasoactive intestinal polypeptide-, neurotensin-, substance P-, gastrin-releasing peptide-, calcitonin-, calcitonin gene related peptide-, and somatostatin-like immunoreactivities in human parathyroid glands. 172 Sep 2

Human small cell lung cancer (SCLC) produces and secretes BN/GRP (bombesin/gastrin releasing peptide). Because BN stimulates the growth of SCLC cells and these cells have receptors for BN-like peptides, it is important to define agents which disrupt this self-promoting autocrine growth cycle. Here, substance P analogues were evaluated as BN receptor antagonists using SCLC cell lines. (D-Arg1, D-Pro2, D-Trp7.9, Leu11) substance P [(APTTL)SP] was one of the more potent analogues tested in inhibiting BN-like peptide receptor binding with an IC50 value of 1 microM. Micromolar concentrations of (APTTL)SP antagonized BN receptor mediated elevation of cytosolic Ca2+ levels and decreased the colony formation in soft agarose. These data suggest that SP analogues function as SCLC BN receptor antagonists and may be useful in disrupting the autocrine growth function of BN-like peptides.
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PMID:Substance P analogues function as bombesin receptor antagonists and inhibit small cell lung cancer clonal growth. 247 67

The GRP receptor mediated growth response in Swiss 3T3 cells has been used to identify BN/GRP antagonists. Analysis of bombesin antagonism by substance P analogues and by truncated GRP analogues revealed that deletion of the C-terminal methionine residue was important for antagonism. Des-Met analogues showing potent antagonist activity in the in vitro 3T3 system (IC50 approximately 2nM) were synthesized. Further structural modification of these peptides led to the identification of (CH3)2CHCO-His-Trp-Ala-Val-D-Ala-His-Leu-NHCH3 (ICI 216140) which reduced bombesin-stimulated rat pancreatic amylase secretion to basal levels when administered subcutaneously at 2.0 mg per kg.
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PMID:N-isobutyryl-His-Trp-Ala-Val-D-Ala-His-Leu-NHMe (ICI 216140) a potent in vivo antaconist analogue of bombesin/gastrin releasing peptide (BN/GRP) derived from the C-terminal sequence lacking the final methionine residue. 255 38

We investigated the production, binding to cell membranes, and influence on cell proliferation of peptides and growth factors in 4 classic, 5 transitional, and 5 variant SCLC cell lines. Glucagon, neurotensin, and TGF-alpha were present in all cell lines. Bombesin was predominantly found in classic cell lines and insulin in variant cell lines. Neurokinin A, calcitonin, CGRP, GHRF, somatostatin, and CNTF were detectable in some cell lines without prevalence for a particular cell type. We could not detect AVP, growth hormone, neuropeptide Y, substance P, VIP, and NGF. Insulin binding sites were present on 11/14 cell lines, and some cell lines specifically bound bombesin, calcitonin, and EGF. Growth effects were detectable for insulin, GRP-related peptides, tachykinins, and VIP. Using serum-free conditions, insulin and VIP had a growth stimulating effect in liquid culture at nanomolar concentrations. Bombesin and neuromedin B stimulated the clonal growth at a concentration of 3-30 nM. The tachykinins neurokinin A, neurokinin B, physalaemin, and eledoisin inhibited the clonal and mass culture growth with a peak effect in the range of 0.1 to 10 pM. Peptide-induced stimulating and inhibiting effects were within a magnitude of 2-fold. All other peptides and growth factors tested, including ACTH, AVP, calcitonin, glucagon, neurotensin, somatostatin, EGF, CNTF, and NGF did not affect the growth of SCLC. We conclude that the growth of SCLC is partly controlled by such peptides in an autocrine/paracrine fashion.
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PMID:Peptides and growth factors in small cell lung cancer: production, binding sites, and growth effects. 283 87

Smooth muscle cells were isolated separately from the longitudinal and circular muscle layers of human jejunum obtained at surgery and used to determine whether amphibian bombesin-14 and 3 mammalian homologues, GRP-(1-27), GRP-(18-27) and neuromedin B, can cause contraction by acting directly on muscle cells. Circular and longitudinal muscle cells contracted identically in response to bombesin-14 (C50 2 x 10(-12) M). The contractile response was not affected by selective muscarinic, opioid, CCK or serotonin antagonists but was inhibited by the substance P (SP) derivative, [D-Arg1, D-Pro2, D-Trp7,9, Leu11]SP. All 3 mammalian bombesins were less potent than bombesin-14. GRP-(1-27) and GRP-(18-27) were equipotent (C50 4 x 10(-11) M) but 20 times less potent than bombesin-14. Neuromedin B (C50 6 x 10(-12) M) was 3 times less potent than bombesin-14. All bombesins, however, were more potent than other enteric neuropeptides (e.g., tachykinins, opioid peptides). The study demonstrates conclusively the ability of bombesins to cause direct contraction of intestinal smooth muscle cells.
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PMID:Identification of bombesin receptors on isolated muscle cells from human intestine. 284 22

High levels of BN/GRP are present in classic SCLC and lung carcinoids, whereas BN immunoreactivity is absent in variant SCLC, adenocarcinoma, large cell carcinoma, squamous cell carcinoma, and mesothelioma cell lines. BN-like peptides are secreted from classic SCLC into the tissue culture medium. The secretion rate of BN-like peptides from cell line NCI-H345 was increased 3-fold by VIP (1 microM). Also, VIP increased the cAMP levels in cell line NCI-H345 by an order of magnitude. Therefore, SCLC cells have functional VIP receptors which regulate the secretion of BN-like peptides. Also, SRIF (100 nM) inhibits the VIP-stimulated increase in cAMP levels and secretion rate of BN-like peptides from SCLC cells. Because BN stimulates colony formation, VIP and/or SRIF may be able to alter the growth of SCLC cells. BN-like peptides are secreted from SCLC cells into the plasma. The levels of BN immunoreactivity in the plasma of SCLC patients with extensive disease is 2- to 40-fold greater than that of patients with limited disease. Secretin infusion into patients with extensive disease produces a transient increase (7-fold) in the plasma concentration of BN-like peptides. BN-like peptides are also present in the CSF of SCLC patients. When released from SCLC cells, BN-like peptides may interact with cell surface receptors. [Tyr4]BN binds with high affinity (Kd = 0.5 nM) to a single class of sites (1500/cell) on cell line NCI-H345. The carboxyl terminus of BN or GRP is essential for high-affinity binding activity. BN-like peptides elevate cytosolic Ca2+ levels as a result of increased phosphatidylinositol turnover. The putative BN receptor antagonist [D-Arg1, D-Pro2, D-Trp7,9, Leu11]substance P inhibits high-affinity [Tyr4]BN binding, the ability of BN to elevate cytosolic Ca2+ levels, and colony formation of SCLC cells. Therefore, BN receptor antagonists may serve as useful agents to inhibit the growth of SCLC.
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PMID:The release of bombesin-like peptides from small cell lung cancer cells. 285 97

A large number of antisera mainly raised against mammalian hormones are tested immunocytochemically on the GEP-endocrine system of mouse and fish (Barbus conchonius). The endocrine pancreas of mouse and fish appeared to contain the same four endocrine cell types; insulin-, glucagon-, PP- and somatostatin-immunoreactive cells. In mouse about 13 GEP endocrine cell types are distinguished: 1. insulin-, 2. somatostatin-, 3. glucagon-, 4. PP-, 5. (entero)glucagon-/PP-like, 6. CCK-like, 7. substance P-, 8. neurotensin-, 9. VIP-, 10. gastrin-, 11. secretin-, 12. beta-endorphin-, 13. serotonin-immunoreactive cells. Based on this and a previous study at least 13 GEP endocrine cell types seems to be present in stomachless fish: 1-9 as described for mouse, 10. (entero)glucagon-like, 11. met-enkephalin, 12. VIP-like, 13. unspecific immunoreactive endocrine cells. Coexistence of glucagon and PP-like peptides is found in the gut and pancreas of mice and in the gut of B. conchonius. In mouse pancreas and fish gut, endocrine cells showing only PP- or glucagon-like immunoreactivity are found too. In mouse stomach some endocrine cells showing only PP-immunoreactivity are demonstrated. In the same region coexistence of C-t-gastrin- and FMRF-amide-immunoreactivity is found in endocrine cells. The importance of these phenomena are discussed. Enteric nerves immunoreactive with antisera raised against substance P and GRP are found in mouse, against somatostatin and met-enkephalin in both mouse and fish and against VIP in fish.
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PMID:Immunocytochemical identification and localization of peptide hormones in the gastro-entero-pancreatic (GEP) endocrine system of the mouse and a stomachless fish, Barbus conchonius. 287 13


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