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)

By use of light microscopic immunohistochemical and lectin histochemical methods, the interrelation of galactose-containing glycoprotein (GCGP), calcitonin gene-related peptide (CGRP)-like, leu-enkephalin (L-ENK)-like, and substance P (SP)-like peptides has been evaluated on consecutive sections of dorsal root ganglia from colchicine-treated rats. The results showed that GCGP, CGRP, L-ENK and SP exist simultaneously in individual neurons of the dorsal root ganglia in rats. Almost all small neurons in dorsal root ganglion contained both GCGP and CGRP. The stronger peanut lectin affinity with small neurons, the weaker CGRP immunoreactivity, and vice versa. Some neurons of medium size were of strong CGRP-like immunoreactivity; however, they lacked in affinity with peanut lectin. The large spinal ganglionic cells rarely showed CGRP immunoreactivity and affinity with peanut lectin. The results suggested that there was a negative interrelation between GCGP and CGRP in small primary sensory neurons. From the above it may be suggested that the GCGP plays an important role in recognizing and transmitting information in primary sensory neurons.
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PMID:Simultaneous existence of galactose-containing glycoprotein and several neuropeptides in DRG of the rat. 137 55

Substance P (SP) is an 11-amino-acid neuropeptide found in sensory neurons in the peripheral nervous system. In addition to having well-characterized functions as a peptide neurotransmitter, it also plays a major role in modulating inflammatory and immune responses. SP can alter the proliferative and physiological responses of both lymphocytes and macrophages. These effects are mediated by specific high-affinity SP receptors which have been characterized both kinetically and biochemically. The principle SP binding protein present on human lymphocyte cell membranes is a 58,000-MW hydrophobic glycoprotein. Cellular responses subsequent to the binding of substance P to its receptor that have been identified in various cell populations include phosphatidyl inositol turnover, arachidonic acid metabolism, immunoglobulin synthesis, and enzyme production and secretion. Evidence also suggests that SP modulation of inflammation is a factor in the pathophysiology of certain diseases such as rheumatoid arthritis.
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PMID:Immunomodulation by tachykinin neuropeptides. 169 81

We measured the intracellular free calcium ion concentration [( Ca2+]i) of acinar cells in isolated feline tracheal submucosal glands in response to secretagogues using the Ca2(+)-sensitive fluorescent dye fura-2. The secretagogues included cholinergic, adrenergic agonists, substance P (SP), and vasoactive intestinal polypeptide (VIP) which induce mucus glycoprotein secretion from feline tracheal submucosal glands. Methacholine (MCh) produced a significant increase in [Ca2+]i of up to 9.8 times that of control in a dose-dependent fashion at concentrations of 10(-8) to 10(-3) M. [Ca2+]i increase by MCh reached a peak within 30 s after stimulation and thereafter showed a sustained rise. In Ca2(+)-free medium, MCh produced an initial transient rise, which was less than 30% of that in a Ca2(+)-containing solution, and which lasted for 60 s with no prolonged sustained rise in [Ca2+]i. Atropine abolished MCh-evoked [Ca2+]i increase. Phenylephrine and SP produced a prolonged increase in [Ca2+]i without an initial transient increase. Phenylephrine (up to 10(-4) M) evoked an increase in [Ca2+]i by up to 240% that of control, which was abolished by prazosin. SP (up to 10(-4) M) also evoked an increase in [Ca2+]i by 155% that of control, which was abolished by atropine. By contrast, both isoproterenol (up to 10(-5) M) and VIP (up to 10(-5) M) failed to alter [Ca2+]i. These findings indicate that the mucus glycoprotein secretion evoked by muscarinic cholinergic, alpha-adrenergic agonist or SP can be mediated by intracellular Ca2+, whereas that by beta-adrenergic agonists or VIP cannot.
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PMID:Intracellular calcium concentration of acinar cells in feline tracheal submucosal glands. 170 76

A large amount of mucus and mucoid impaction are observed in the autopsied lungs of bronchial asthmatics. It is possible that mucus hypersecretion and accumulation of intrabronchial mucus result in bronchial obstruction and structural bronchial hyperresponsiveness. Bronchial gland plays a main role in human airway secretion. We describe here some results using isolated gland preparation which enable us to examine airway mucus secretion in a well-defined condition. Chemical mediators released from mast cells augment the secretory responses induced by cholinergic nerve stimulation through accelerated acetylcholine release in the nerve terminals. PAF produces an increase in mucus glycoprotein secretion in the presence of platelets mainly through the thromboxane release from platelets. Substance P which is released by an axon reflex in response to various stimuli and inflammations in the airways, also produced an increase in mucus secretion. Epithelial cells release an inhibitory factor to mucus glycoprotein secretion from bronchial glands. Epithelial cell damages due to inflammation in the airways may induced a reduction of the inhibitory factor release in bronchial asthmatics, resulting in mucus hypersecretion.
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PMID:[Airway hyperresponsiveness and mucus secretion]. 170 51

Our study using feline tracheal isolated submucosal gland preparation has revealed that substance P (SP) produces an increase in submucosal gland secretion through the actions of both mucus ejection by glandular contraction and macromolecule secretion from secretory cells, and that the two actions are both mediated by a peripheral cholinergic action. In contrast, SP has no significant effect on macromolecule secretion from secretory cells in tracheal explants, probably because of epithelial suppression. Our study using an isolated gland preparation has also indicated that VIP potentiates mucous glycoprotein secretion induced by cholinergic stimulation through an interaction between muscarinic and VIP receptors in secretory cells. However, VIP failed to induce any significant glandular contraction or relaxation, indicating a lack of VIP receptors or a difference in the subtypes of muscarinic receptors in myoepithelial cells in submucosa glands.
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PMID:Neuropeptides and airway submucosal gland secretion. 170 51

Antisera raised against the fixation products of L-glutamate and L-aspartate were used, singly or in combination, to study the ultrastructural localization of the amino acids in the rat dorsal horn, with post-embedding immunogold techniques. Immunostaining for each of the amino acids was also combined with immunolocalization of GABA, an important inhibitory neurotransmitter in the spinal cord, or synaptophysin, a synaptic vesicle glycoprotein. In addition, we examined the localization of glutamate immunoreactivity in relation to that of calcitonin-gene related peptide and substance P, two neuropeptides present in high concentrations in the dorsal horn. Glutamate- and aspartate-immunoreactive neuronal cell bodies, dendrites, axons and terminals were apparent in the first three laminae of the dorsal horn. In somatic and dendritic profiles, the immunolabel was present over the general cytoplasm and mitochondria; in the terminals, it was found over small, agranular vesicles, mitochondria and, at times, synaptic densities. Quantitative estimation indicated that the colloidal gold density in the glutamate-immunoreactive terminals was five-fold more than in any other neuronal profile. Both glutamate- and aspartate-immunopositive terminals made asymmetric synaptic contacts onto unlabelled dendrites; glutamate-positive terminals often formed the core of type I and II glomeruli. After double labelling of the same sections, glutamate and aspartate immunoreactivities consistently occurred in different axonal and terminal profiles. In these preparations, it was clearly seen that glutamate-immunoreactive terminals were far more numerous than (more than 10-fold) those immunoreactive for aspartate. Double labelling for glutamate or aspartate and GABA also revealed distinct staining of different terminals. Simultaneous immunolocalization of each of the amino acids and synaptophysin showed the amino acid and glycoprotein immunoreactivities co-localized in small, agranular vesicles in immunoreactive terminals. Finally, triple labelling of the same sections for glutamate, calcitonin gene-related peptide and substance P revealed that glutamate was often co-localized with either of the two neuropeptides in the same axonal boutons; terminals that showed simultaneous labelling for glutamate, calcitonin gene-related peptide and substance P were also noted. In all cases, the glutamate immunoreactivity was restricted to small, clear vesicles whereas the neuropeptide immunoreactivities were present in larger, dense-cored vesicles. Our observations demonstrate that there is an abundant glutamate immunoreactivity in the superficial layers of the rat dorsal horn, localized in neuronal profiles distinct from those containing aspartate or GABA.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Ultrastructural visualization of glutamate and aspartate immunoreactivities in the rat dorsal horn, with special reference to the co-localization of glutamate, substance P and calcitonin-gene related peptide. 171 Nov 77

Neurotensin (NT) endopeptidase (EC 3.4.24.16) has been purified about 800-fold from pig brain by four sequential chromatographic steps depending on ion-exchange and hydrophobic interactions. Two types of preparation were studied: one from a Triton X-100-solubilized membrane fraction, and the other from the soluble fraction containing 90% or more of the total activity in the homogenate. NT endopeptidase activity was monitored by high-precision liquid chromatography of the two peptide products, characterized as NT-(1-10) and NT-(1-8), resulting from cleavage of the Pro10-Tyr11 and Arg8-Arg9 bonds respectively. As purification proceeded, from both membranes and cytosol, the yield of the two products achieved a constant ratio of 5:1 and this ratio was reproduced in repeated purifications. However, a distinct peptidase which hydrolysed exclusively at the Arg8-Arg9 bond was partially resolved from NT endopeptidase by chromatography on hydroxyapatite, and this activity was further purified and assigned to endopeptidase-24.15 (EC 3.4.24.15). SDS/PAGE of both preparations of neurotensin endopeptidase revealed a major band of apparent Mr 75000, and treatment of the membrane-associated form with N-Glycanase gave no evidence that the enzyme was a glycoprotein. The membrane-associated and cytosol forms of NT endopeptidase activities, monitored for both NT-(1-10) and NT-(1-8) products, were compared in their responses to 1,10-phenanthroline, EDTA, dithiothreitol (DTT) and some synthetic site-directed inhibitors of endopeptidase-24.15 or peptidyl dipeptidase A. The effects revealed no significant differences between the two preparations, nor did the reagents discriminate between the activities generating the two NT fragments. The partially purified form of endopeptidase-24.15 was also included in this comparison: while some responses were similar, this peptidase was distinguishable in its activation by DTT and its relative resistance to inhibition by EDTA. Both forms of NT endopeptidase were found to hydrolyse other substrates, including Boc-Phe-Ala-Ala-Phe-4-aminobenzoate, bradykinin and substance P (these at faster rates than neurotensin), as well as dynorphin A-(1-8) and luliberin. The bonds hydrolysed in these neuropeptides, as well as in angiotensins I and II and alpha-neoendorphin, were defined. These studies confirm that NT endopeptidase is distinct from endopeptidase-24.15. They further show that the former is a soluble enzyme, not an integral membrane protein, that it is not peptide-specific and that it might be more appropriately named. enzyme, not an integral membrane protein, that it is not peptide-specific and
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PMID:Purification and properties of a neurotensin-degrading endopeptidase from pig brain. 190 21

Proteolytic processing enzymes are required to convert the enkephalin precursor to active opioid peptides. In this study, a novel 33-kDa thiol protease that cleaves complete precursor in the form of [35S]methionine preproenkephalin was purified from bovine adrenal medullary chromaffin granules. Chromatography on concanavalin A-Sepharose and Sephacryl S-200, chromatofocusing, and chromatography on thiopropyl-Sepharose resulted in an 88,000-fold purification with a recovery of 35% of enzyme activity. The thiol protease is a glycoprotein with a pI of 6.0. It cleaves [35S]methionine preproenkephalin with a pH optimum of 5.5, indicating that it is functional at the intragranular pH of 5.5-6.0. Interestingly, production of trichloroacetic acid-soluble products was optimal at pH 4.0, suggesting that processing of initial precursor and intermediates may require slightly different pH conditions. The protease requires dithiothreitol for activity and is inhibited by the thiol protease inhibitors iodoacetate, p-hydroxymercuribenzoate, mercuric chloride, and cystatin. These properties distinguish it from other thiol proteases (cathepsins B, H, L, N, and S), indicating that a unique thiol protease has been identified. The enzyme converted [35S]cysteine preproenkephalin (possessing [35S]cysteine residues specifically within the precursor's NH2-terminal segment) to 22.1-, 21.6-, 17.7-, 17.3-, and 15.0-kDa intermediates that contain the precursor's NH2-terminal segment; proenkephalin in vivo is converted to similar intermediates. The enzyme cleaves peptide F at Lys-Arg and Lys-Lys dibasic amino acid sites to generate methionine enkephalin and intermediates. The appropriate vesicular localization, pH optimum, proteolytic products, and cleavage site specificity suggest that this thiol protease may be involved in enkephalin precursor processing. Most interestingly, [35S]methionine beta-preprotachykinin, a precursor of substance P, is minimally cleaved, suggesting that the thiol protease may possess some selectivity for the enkephalin precursor.
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PMID:Purification and characterization of a novel thiol protease involved in processing the enkephalin precursor. 202 53

The diagnosis of "poorly differentiated" carcinoma was made in 47 of 683 colon cancers on the basis of conventional light microscopy which showed poorly defined glands, solid architecture or variable admixtures thereof. Samples from 44 of these 47 tumors were assessed by immunohistochemical analysis for the presence of neuroendocrine (NE) antigens. Paraffin sections were immunostained with antibodies to NSE, chromogranin, serotonin, VIP, substance P and somatostatin. Additional sections were also stained with monoclonal antibody (Mab) A-80 that recognizes a glycoprotein related to exocrine (EX) differentiation. Based on our findings, the tumors were phenotypically reclassified as follows: I) pure EX (n = 8), II) pure NE (n = 4), III) mixed EX-NE carcinomas (n = 23), and IV) predominantly EX carcinomas with occasional NE cells (n = 9). Survival among groups II and III appeared to be less than group I and survival in group IV was significantly less than group I. Survival among the four pure NE (group II) and 11 predominantly NE mixed carcinomas (group III) taken together was significantly less than the pure EX carcinomas. This study indicates: 1) The incidence of NE differentiation in tumors of the colon and rectum is higher than previously believed. 2) The poorly differentiated colon carcinomas comprise four distinct groups: pure EX, pure NE, mixed EX-NE carcinomas, and predominantly EX carcinomas with a NE cell subpopulation. 3) The presence of NE differentiation or of a NE cell subpopulation in colon carcinoma appears to be associated with a poorer prognosis.
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PMID:Neuroendocrine differentiation in "poorly differentiated" colon carcinomas. 236 84

The action of substance P on glycoprotein secretion from acinar cells of the rat submandibular gland was described in this report. Salivation elicited by i.v. injection of 0.5 to 20 micrograms/kg of substance P was increased dose-dependently, and its flow rate was highest at the first 1 min. Major glycoprotein species secreted into saliva by substance P-stimulus were shown to be electrophoretically identical with those found in acini, but not granular convoluted tubules. These results support the view that substance P acts on acinar cells of the submandibular gland and stimulates secretion of saliva from the cells.
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PMID:Effects of substance P on glycoprotein secretion from acinar cells of the rat submandibular gland. 243


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