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)

Substance P (SP) and thyrotrophin-releasing hormone (TRH) are co-localized with serotonin (5-HT) in cells of the medullary raphe nuclei. In order to examine the factors that control development of multiple neurotransmitters within individual brain nuclei, we have grown presumptive raphe nuclei in organotypic tissue culture, an environment in which mammalian embryonic brain is easily accessible and manipulable. Tissue was obtained from E13 mice. A discrete midline segment of the rhombencephalon was dissected intact or was separated into 'rostral' (RR) and 'medullary' (MR) fragments. Tissue was explanted onto collagen coverslips and grown for up to two weeks in Maximow depression chambers. Tryptophan hydroxylase (TPH), the rate-limiting enzyme in 5-HT biosynthesis, was barely detectable at explantation. During the first week in culture, however, TPH activity increased 7-fold. After two weeks, TPH activity increased almost 2.5-fold above the one-week level. Immunocytochemical analysis of the cultures confirmed a widespread distribution of 5-HT-positive cells and fibers throughout the explant. SP, monitored by radioimmunoassay, was detected after two days in culture, and attained a level of 111.7 +/- 9.8 pg/culture after two weeks. TRH activity was similarly elevated after two weeks in vitro. Therefore, developmental increases in TPH, SP, and TRH occurred in culture, mimicking the condition in vivo. RR and MR fragments, when grown apart on separate coverslips, developed 1.57-2.26 times the TPH activity that developed in the undivided piece. Inclusion of 1 microM pargyline in the fragments restored TPH to control levels. The effect of pargyline was blocked by methiothepin, suggesting autoreceptor-mediated regulation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Development of serotonin, substance P and thyrotrophin-releasing hormone in mouse medullary raphe grown in organotypic tissue culture: developmental regulation by serotonin. 246 25

Microscopic studies have shown the saccopleural membrane in the respiratory system of the domestic fowl to consist of a sheet of three dense layers of collagen fibres covered dorsally and ventrally by mainly simple squamous epithelium. On the ventral surface, which faces into the caudal thoracic air sac, there are occasional ridges of pseudostratified ciliated epithelium. Many nerve bundles are present throughout the membrane, the larger bundles of myelinated and unmyelinated axons being confined to the lamina propria under the dorsal epithelium (parietal pleura). In addition to axonal profiles with the ultrastructural appearance of cholinergic or adrenergic axons, peptidergic-type axons were identified. Immunofluorescence studies demonstrated VIP-, substance P-, somatostatin- and enkephalin-immunoreactive fibres in the membrane. Although it has been suggested that receptors may be present in this region of the respiratory system, none of the axons have features suggestive of sensory terminals, although many axonal profiles are closely associated with the epithelia where no obvious effector cells are present.
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PMID:The structure and innervation of the saccopleural membrane of the domestic fowl, Gallus gallus: an ultrastructural and immunohistochemical study. 365 25

F9 line embryonal carcinoma cells were induced to differentiate into neural direction by long-term treatment of monolayer cultures with retinoic acid and dibutyryl cyclic AMP. Bi- and multi-polar cells appeared, expressing acetylcholinesterase and neurofilament proteins but not markers of glial differentiation including GFA-protein. Nerve growth factor combined with both retinoic acid and dibutyryl cyclic AMP greatly enhanced the development of neuron-like morphology and induced expression of immunoreactivity to tyrosine hydroxylase as well as to Leu-encephalin-like peptides. Similarly, serotonin-like immunofluorescence but not substance P-like immunoreactivity was demonstrable in such cultures. In addition, synaptic-like vesicles were often found in the processes. Analysis of matrix expression in neuronally differentiated F9 cells revealed marked increase in laminin production, as judged by immunofluorescence and immuno-electron microscopy, but no demonstrable intracellular staining for fibronectin or type IV collagen. The results with neuronal cells contrast with the expression of all the three matrix components in endodermally differentiating F9 cells in the same cultures.
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PMID:Neuronal differentiation in F9 embryonal carcinoma cells. 610 Jan 70

Substance P (SP), the putative neuropeptide mediator of pain sensation, is contained in small dorsomedial sensory neurons of the dorsal root ganglion. Using different culture techniques and a sensitive radioimmunoassay for SP, we studied the ontogeny and regulation of this functionally important neurotransmitter in these neurons, obtained from neonatal rats. In ganglion explants grown by two different techniques, SP increased two- to threefold during the first week in culture. This rise was predominantly due to mechanisms intrinsic to the ganglion since it occurred in a fully defined medium, in the absence of added nerve growth factor (NGF). Blockade of protein synthesis with cycloheximide prevented the increase in SP suggesting that ongoing protein synthesis was necessary. Furthermore, depolarization with veratridine blocked the increase in SP, an effect which was reversed by tetrodotoxin, suggesting that transmitter characteristics in sensory neurons may be regulated by depolarization and/or transmembrane sodium flux. After a week in culture on a collagen substratum, supplementary NGF was necessary for the continued rise in SP. However, raising the dose of the trophic factor had no incremental effect on SP content, suggesting that NGF was acting primarily on neuronal survival. To approach such questions at the cellular level, ganglia were dissociated and grown in cell culture. In all cultures, SP increased 1.5-fold during the first day. In the absence of NGF, however, SP and cell numbers fell progressively after the second day. NGF elicited parallel increases in cell survival and SP content, supporting the suggestion that NGF acts primarily through neuronal survival to increase SP. Veratridine blocked the increase in SP in a tetrodotoxin-reversible manner, without affecting neuronal survival, indicating that the effects of these agents do not depend on normal ganglionic cellular architecture. Consequently, depolarization probably affects ganglionic sensory neurons directly. Our studies suggest that the development of transmitter characteristics in primary sensory neurons may be regulated by multiple factors, including neuronal activity as well as trophic agents such as NGF.
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PMID:Development and regulation of substance P in sensory neurons in vitro. 620 Mar 74

A post-proline cleaving enzyme [prolyl endopeptidase, EC 3.4.21.26] was purified about 3,700-fold from an extract of bovine brain by a series of column chromatographies on DEAE-Sephadex, hydroxyapatite and PCMB-T-Sepharose, and gel filtration on Sephadex G-200 using N-carbobenzoxy-Gly-Pro-beta-naphthylamide (Z-Gly-Pro-2-NNap), thyrotropin releasing hormone (TRH) and oxytocin as substrates. The purified enzyme appeared homogeneous as judged by disc gel and SDS gel electrophoreses. The enzyme was most active at pH 7.5 and 7.2 with Z-Gly-Pro-2-NNap and TRH, respectively, and hydrolyzed peptide bonds involving Pro-X (X=amino acid, peptide, ester and amide) bonds of synthetic substrates, oxytocin, vasopressin, neurotensin, substance P, tuftsin, bradykinin, and insulin B chain. However, the enzyme was inert toward collagen, gelatin, and casein. The enzyme was completely inactivated by diisopropylphosphorofluoridate (DFP), Z-Gly-Pro-chloromethyl ketone and p-chloromercuribenzoate (PCMB), while it was not inhibited by phenylmethane sulfonylfluoride (PMSF) or metal chelators. Determination of the amino acid composition revealed that the enzyme contained 25 half-cystines. Modification of three cysteine residues of the enzyme by PCMB led to complete inactivation. The isoelectric point of the enzyme was 4.8, and the molecular weight was estimated to be 76,000 by ultracentrifugal analysis and 75,000-74,000 by both gel filtration and sodium dodecyl sulfate (SDS) gel electrophoresis, suggesting that the enzyme is present as a monomer. These results indicate that the post-proline cleaving enzyme from bovine brain is very similar to those previously purified from lamb brain and kidney in its enzymatic properties, substrate specificity and physicochemical properties, in sharp contrast with the results obtained by Tate, who reported that the bovine brain prolyl endopeptidase was inert toward oxytocin, vasopressin and bradykinin.
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PMID:Post-proline cleaving enzyme (prolyl endopeptidase) from bovine brain. 636 Oct 10

Specimens of hypertrophic scar tissue (n = 9), non-hypertrophic, flat scar tissue (n = 5) and control skin (n = 3) were obtained from eight adult females (aged 22-56) and three adult males (aged 22-59). The specimens were studied histologically and immunohistochemically for vasoactive intestinal polypeptide, neuropeptide Y, calcitonin gene-related peptide, substance P, somatostatin, [Met]enkephalin, [Leu]enkephalin, and the enzyme dopamine beta-hydroxylase. The non-hypertrophic scar tissues were not dissimilar to the control tissue, but contained connective tissue in bundles with a greater number of collagen fibres. In the hypertrophic scar tissue of some patients, the dermis contained adipose tissue displaced upwards from the hypodermis. The connective tissue contained densely packed collagen fibres and fibroblasts; this region was devoid of hair follicles, sweat glands and blood vessels, although they were observed in the region of loosely packed connective tissue. The normal skin contained all the neuropeptides studied, except somatostatin-, and dopamine beta-hydroxylase-immunoreactive nerves, which were seen as single fibres or in nerve bundles, and were associated with blood vessels in the dermis. Neuropeptide Y-immunoreactive nerves were found in the arrector pili muscle, and neuropeptide Y-, vasoactive intestinal polypeptide-, calcitonin gene-related peptide-, [Met]enkephalin- and dopamine beta-hydroxylase-containing nerves were found within sweat glands. In patients with flat, non-hypertrophic scar tissue, neuropeptides and dopamine beta-hydroxylase-containing nerves were absent. In patients with hypertrophic scars, the density of neuropeptide Y-, vasoactive intestinal polypeptide-, substance P-, calcitonin gene-related peptide- and dopamine beta-hydroxylase-immunoreactive nerves was greater in the dermis when compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neuropeptide-containing nerves in painful hypertrophic human scar tissue. 751 32

Matrix metalloproteinase-9 (MMP-9) is secreted from cells and, once activated, is thought to degrade collagen in the extracellular matrix. Because collagen is not readily localized where neurons have been shown to produce MMP-9 in the human brain, the ability of this enzyme to degrade bioactive peptides was investigated with representative tachykinin peptides [substance P (SP), neurokinin A, neurokinin B, and kassinin]. Latent MMP-9 (94 kDa) was purified from the human cell line HL-60 and converted to an intermediary active form (84 kDa) with p-aminophenylmercuric acetate. This active form of MMP-9 degraded SP with a kcat/Km of 170 mM-1 min-1, which is 30-fold greater than the previously reported value for a representative collagen-derived peptide. The major digestion products were identified as SP and SP, which were derived from cleavage of the Gln6-Phe7 bond. Minor products were also generated from cleavage of the Gly9-Leu10 bond. The other representative tachykinin peptides were cleaved at rates > 10-fold slower than that of SP. The 84-kDa peptidase was also active as a gelatinase. Longer treatment of MMP-9 with p-aminophenylmercuric acetate caused the conversion of the 84-kDa enzyme to the established 68-kDa active form; however, the rate of SP degradation did not increase. Because MMP-9 is produced by neurons of the CNS, these results suggest a possible regulatory role for the enzyme in interacellular communication by altering the availability of bioactive peptides.
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PMID:The 84-kDa form of human matrix metalloproteinase-9 degrades substance P and gelatin. 753 11

Four different gamma-(glutamyl5)amine derivatives of substance P (SP) were synthesized in vitro in the presence of purified guinea pig liver transglutaminase and Ca2+. The 1,3-diaminopropane, spermidine, spermine (Spm), and monodansylcadaverine adducts of the neuropeptide were purified by HPLC on a reversed-phase column and characterized by fast atom bombardment mass spectrometry. The gamma-(glutamyl5)Spm derivative of SP (Spm-SP) was found to be able, like the parent neuropeptide, to provoke rabbit aorta relaxation, to decrease rat arterial blood pressure, and to inhibit collagen-induced platelet aggregation. Unlike SP, only a weak inflammatory response was observed when Spm-SP was injected in the rat hind limb. All these effects were found to be prevented by N omega-nitro-L-arginine methyl ester, a well-known nitric oxide synthesis inhibitor. In contrast, Spm-SP was completely ineffective in contracting guinea pig ileal segments, thus confirming our preliminary observations indicating that Spm-SP does not evoke SP-like spasmogenic effects on isolated smooth muscle preparations. The specificity of the effects due to the selective introduction of a Spm moiety at the glutamine5 level was demonstrated by the SP agonist pharmacological profile of the other gamma-(glutamyl5)amine derivatives tested. These results suggest that neurokinin receptors could be differentiated by their capacity to respond to Spm-SP.
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PMID:Neurokinin receptors could be differentiated by their capacity to respond to the transglutaminase-synthesized gamma-(glutamyl5)spermine derivative of substance P. 754 Jun 66

Congenital esophageal stenosis (CES) is a rare disorder with narrowed esophageal lumen that presents as dysphagia from childhood and that is often associated with tracheobronchial remnants or webs. The pathogenesis of CES is unknown. The aim of this study was to examine the histological and immunohistochemical features of CES. Esophagi from 2 young adults with CES and 3 controls with no motility disorders underwent routine H&E staining, trichrome staining for collagen, and detailed immunocytochemical studies for general neuronal markers (protein gene product 9.5, neuron-specific enolase, and S-100) and neurotransmitters (vasoactive intestinal polypeptide, substance P, and galanin) and nitric oxide synthase by beta-nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase and a specific NO synthase antibody. Quantitative experiments compared the numbers of myenteric neurons and amounts of fibers at the circular muscle. CES esophagi showed infiltration of neutrophils in the myenteric plane, without any increase in collagen. NADPH-diaphorase histochemistry showed a significant reduction of myenteric nitrinergic neurons (7 +/- 3.4 vs. 2.7 +/- 1.8 neurons per high-power field) and fibers at the circular muscle. Other peptidergic neurons studied were not significantly reduced in CES. The specific total lack of NO inhibitory innervation may be an important mechanism in the pathogenesis of stenosis and aperistalsis of the esophagus in this disorder.
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PMID:Peptidergic and nitrinergic denervation in congenital esophageal stenosis. 754 Oct

A unique group of neurons in the submucous plexus of the gastrointestinal tract in guinea pigs was studied using (1) Nissl staining and an enzyme histochemical technique for acetylcholinesterase (AChE), (2) immunohistochemical methods for the localisation of neuron specific enolase (NSE) and neuropeptides, including vasoactive intestinal peptide (VIP), substance P (SP), somatostatin (SOM), calcitonin gene-related peptide (CGRP), leu-enkephalin (leu-ENK), neuropeptide (NPY) and cholecystokinin (CCK), (3) a fluorescence tracer technique involving the intraperitoneal (i.p.) injection of fluorogold, and (4) normal electron microscopy. The results showed that these neurons were distributed singly or in groups in the submucosa. They were closely adherent to the outer walls of lymphatic vessels, some appearing to protrude into the lumen. Ultrastructurally, only a thin layer of basal lamina and some collagen fibrils intervened between the endothelia of the lymphatic vessels and these neurons. Based on their synaptic contacts and the features of their content of synaptic vesicles, at least 4 types of axon terminal forming synaptic contacts with the 'lymphatic vessel-associated neurons' (LV-AN) were identified. The sources of origin of these terminals remains uncertain although it is speculated that they may be derived from vagal efferents or of intrinsic origin from the neighbouring neurons. All the LV-AN showed AChE and NSE positive reactions, but only a varying number were positive for VIP, SP, SOM, ENK, CGRP, CCK or NPY. The LV-AN were labelled with fluorogold injected i.p.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Studies of the lymphatic vessel-associated neurons in the intestine of the guinea pig. 755 16


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