UNIPROT:P20366 - FACTA Search

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Query: UNIPROT:P20366 (substance P)
21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

KP-102, a second generation growth hormone-releasing peptide, specifically bound to the human neuroblastoma cell line, EP-1, cultured in vitro with a Kd value comparable to that in cell membranes of rat pituitary and hypothalamus. By crosslinking study, the molecular size of the KP-102-receptor complex was found to be approximately 80kDa. Substance P analogue, as well as nonpeptidyl antagonists of the neurokinin receptor, competed with KP-102 in its binding to EP-1 cells, although neither substance P nor substance K affected the binding. These results suggest that KP-102 binds to a receptor-like molecule resembling neurokinin receptor.
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PMID:Neurokinin receptor antagonists inhibit the binding of growth hormone-releasing peptide to EP-1 human neuroblastoma cells. 767 51

1. The 5-HT3 receptor-mediated cation influx into N1E-115 mouse neuroblastoma cells has been studied by the use of the organic cation [14C]-guanidinium. 2. 5-Hydroxytryptamine (5-HT, 30 microM) caused a time-dependent influx of [14C]-guanidinium which, in contrast to the influx elicited by veratridine (100 microM), was not inhibited by tetrodotoxin (TTX, 10 microM). The 5-HT-induced influx was potentiated by substance P and inhibited by ondansetron. 3. 5-HT and the selective 5-HT3 receptor agonists, m-chloro-phenylbiguanide, phenylbiguanide and 2-methyl-5-HT caused bell-shaped concentration-response curves; the rank order of potency was m-chloro-phenylbiguanide > 5-HT > phenylbiguanide = 2-methyl-5-HT. Among these agonists, 5-HT elicited the highest influx of [14C]-guanidinium. 5-Methoxytryptamine, an agonist at 5-HT4 receptors, showed no effect. 4. The [14C]-guanidinium influx induced by 100 microM 5-HT was not affected by methysergide (10 microM) and ketanserin (10 microM) but was inhibited by 5-HT3 receptor antagonists with the following rank order of potency: ICS 205-930 > ondansetron > MDL 72222 >> metoclopramide. 5. The 5-HT-induced [14C]-guanidinium influx was increased in the absence of Ca2+ and/or Na+ and by a reduction of the temperature from 36 degrees to 20 degrees C. 6. Preincubation with 5-HT (100 microM) caused a time-dependent and rapidly reversible decrease of the 5-HT-induced [14C]-guanidinium influx. 7. It is concluded that [14C]-guanidinium influx measurement in N1E-115 cells is a convenient method to study properties of the cation channel of the 5-HT3 receptor. This influx is independent of the fast sodium channel.
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PMID:Characterization of 5-HT3 receptors of N1E-115 neuroblastoma cells by use of the influx of the organic cation [14C]-guanidinium. 768 May 94

In the presence of substance P (SP; 10 microM), serotonin (5-HT; 1 microM) triggered a cation permeability in cells of the hybridoma (mouse neuroblastoma x rat glioma) clone NG 108-15 that could be assessed by measuring the cell capacity to accumulate [14C]guanidinium for 10-15 min at 37 degrees C. In addition to 5-HT (EC50 0.33 microM), the potent 5-HT3 receptor agonists 2-methyl-serotonin, phenylbiguanide, and m-chlorophenylbiguanide, and quipazine, markedly increased [14C]guanidinium uptake in NG 108-15 cells exposed to 10 microM SP. In contrast, 5-HT3 receptor antagonists prevented the effect of 5-HT. The correlation (r = 0.97) between the potencies of 16 different ligands to mimic or prevent the effects of 5-HT on [14C]guanidinium uptake, on the one hand, and to displace [3H]zacopride specifically bound to 5-HT3 receptors on NG 108-15 cells, on the other hand, clearly demonstrated that [14C]guanidinium uptake was directly controlled by 5-HT3 receptors. Various compounds such as inorganic cations (La3+, Mn2+, Ba2+, Ni2+, and Zn2+), D-tubocurarine, and memantine inhibited [14C]guanidinium uptake in NG 108-15 cells exposed to 5-HT and SP, as expected from their noncompetitive antagonistic properties at 5-HT3 receptors. However, ethanol (100 nM), which has been reported to potentiate the electrophysiological response to 5-HT3 receptor stimulation, prevented the effects of 5-HT plus SP on [14C]guanidinium uptake. The cooperative effect of SP on this 5-HT3-evoked response resulted neither from an interaction of the peptide with the 5-HT3 receptor binding site nor from a possible direct activation of G proteins in NG 108-15 cells. Among SP derivatives, [D-Pro9]SP, a compound inactive at the various neurokinin receptor classes, was the most potent to mimic the stimulatory effect of SP on [14C]guanidinium uptake in NG 108-15 cells exposed to 5-HT. Although the cellular mechanisms involved deserve further investigations, the 5-HT-evoked [14C]guanidinium uptake appears to be a rapid and reliable response for assessing the functional state of 5-HT3 receptors in NG 108-15 cells.
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PMID:Characteristics of [14C]guanidinium accumulation in NG 108-15 cells exposed to serotonin 5-HT3 receptor ligands and substance P. 768 66

A case of a parotid mass in a 2-year-old boy, postoperatively diagnosed as neuroblastoma, a rare tumour not previously reported in the parotid gland is presented. The neoplasm developed within the parotid gland as a painless mass without regional lymphadenopathy. Histopathologically, the tumour showed primitive nerve cells-neuroblasts-with round or oval dark basophilic nuclei and scanty cytoplasm. The cells were arranged in circular rosettes around an eosinophilic mass consisting of very fine filaments originating in the tumour cells or papillary configuration and sometimes scattered in the poorly developed stroma. Immunohistochemical evaluation of the tumour showed a positive immunoreactivity for vimentin, alpha and beta subunits of S-100 protein, neurone-specific enolase (NSE), substance P, met-enkephalin and chromogranin but cytokeratins, desmin, actin, myosin, glial fibrillary acidic protein (GFAP) and calcitonin gene related peptide (CGRP) were negative. The histopathological and immunohistochemical findings conclude a diagnosis of neuroblastoma of the parotid gland.
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PMID:Neuroblastoma of parotid gland: report of a case and immunohistochemical characteristics. 770 7

1. Synthetic amyloid beta-peptide was toxic to NB41A3 neuroblastoma cells in serum-free culture as judged by decreasing cell numbers and release of the cytosolic enzyme, lactic dehydrogenase. 2. Without amyloid beta-peptide, bovine serum albumin increased the number of cells surviving in culture. 3. In the presence of amyloid beta-peptide, BSA appeared to potentiate the amyloid beta-peptide toxicity. 4. The toxic dose response for amyloid beta-peptide varied between different cell lines (NB41A3, NB2a and IMR32), in a range of 100-1000 nM amyloid beta-peptide. 5. Amyloid beta-peptide toxicity was inhibited by the concurrent treatment of the cells with the tachykinin physalaemin with an ED50 of 10(-6) M.
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PMID:Comparative toxicity of amyloid beta-peptide in neuroblastoma cell lines: effects of albumin and physalaemin. 790 10

A new metallo-endopeptidase which hydrolyzes atrium natriuretic factor (ANF) has been isolated from human neuroblastoma NB-OK-1 cells. In the present study we show that this metallo-endopeptidase is also present in several other human neuroblastoma cell lines, which include CHP 100, SH-SY5Y, SK-N-BE(2), BE(2)-C and BE(2)M-17. Additionally, we show that this endopeptidase activity is reduced to about 20% of the control during retinoic acid (RA)-induced neuronal differentiation in the RA-sensitive SK-N-BE(2) cells, but not in the RA-resistant BE(2)-M17 cells. This suggests that the inhibition is related to neuronal differentiation and not to a direct effect of 5 microM RA on the enzyme activity. This new enzyme is clearly distinct from neutral endopeptidase (NEP, EC 3.4.24.11) and angiotensin-converting enzyme (ACE,EC 3.4.15.1), since specific inhibitors for these endopeptidases (10 microM phosphoramidon and 1 mM captopril, respectively) had no effect on their activity. However, this enzyme was inhibited 100% by 10 mM o-phenanthroline showing an inhibitory spectrum similar to that of another novel metallo-endopeptidase recently isolated in our laboratory from Xenopus laevis skin secretion. Although the physiological function of this new enzyme in human neuroblastoma cells is not known at the present time, we suggest that it may participate in inactivation of neuropeptides such as atrium natriuretic factor (ANF), substance P, somatostatin-14 and bradykinin in vivo.
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PMID:Human neuroblastoma cells express a novel metallo-endopeptidase activity able to inactivate atrial natriuretic factor: inhibition during retinoic acid-induced differentiation. 813 18

The action of neuropeptides at the synapse is terminated through enzymatic degradation by membrane-bound proteases. We defined and purified membrane-bound proteases functioning at the initial stage of degradation of four neuropeptides. 1. Substance P-degrading endopeptidases isolated from the rat brain and pig striatum showed similar properties to those of endopeptidase-24.16 (neurolysin) except for cleavage sites of substance P. 2. LHRH fragment (1-5)-generating endopeptidases isolated from the neuroblastoma cells and rat brain showed similar properties to those of endopeptidase-24.15 (thimet oligopeptidase). 3. One of two dynorphin-degrading cysteine proteases isolated from neuroblastoma cells showed strict specificity toward the Arg-Arg residues. 4. Endopeptidase-24.11 (neprilysin) isolated from the rat brain was identified as a somatostatin-degrading enzyme.
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PMID:[Membrane-bound proteases involved in neuropeptide degradation in the brain]. 836 28

1. The in vitro and in vivo pharmacology of GR203040 ((2S, 3S)-2-methoxy-5-tetrazol-1-yl-benzyl-(2-phenyl-piperidin-3-y l)-amine), a novel, highly potent and selective non-peptide tachykinin NK1 receptor antagonist, was investigated in the present study. 2. GR203040 potently inhibited [3H]-substance P binding to human NK1 receptors expressed in Chinese hamster ovary (CHO) and U373 MG astrocytoma cells, and NK1 receptors in ferret and gerbil cortex (pKi values of 10.3, 10.5, 10.1 and 10.1 respectively). GR203040 had lower affinity at rat NK1 receptors (pKi = 8.6) and little affinity for human NK2 receptors (pKi < 5.0) in CHO cells and NK3 receptors in guinea-pig cortex (pKi < 6.0). With the exception of the histamine H1 receptor (pIC50 = 7.5). GR203040 had little affinity (pIC50 < 6.0) at all non-NK1 receptors and ion channels examined. Furthermore, GR203040 produced only weak inhibition of Na+ currents in SH-SY5Y neuroblastoma and superior cervical ganglion cells (pIC50 values < 4.0). GR203040 produced only weak antagonism of Ca(2+)-evoked contractions of rat isolated portal vein (pKn = 4.1). The enantiomer of GR203040, GR205608 (2R, 3R)-2-methoxy-5-tetrazol-1-yl-benzyl-(2-phenyl-piperidin-3-y l)-amine), had 10,000 fold lower affinity at the human NK1 receptor expressed in CHO cells (pKi = 6.3). 3. In gerbil ex vivo binding experiments, GR203040 produced a dose-dependent inhibition of the binding of [3H]-substance P to cerebral cortical membranes (ED50 = 15 micrograms kg-1 s.c. and 0.42 mg kg-1 p.o.). At 10 micrograms kg-1 s.c., the inhibition of [3H]-substance P binding was maintained for > 6 h. In the rat, GR203040 was less potent (ED50 = 15.4 mg kg-1 s.c.) probably reflecting, at least in part, its lower affinity at the rat NK1 receptor. 4. In guinea-pig isolated ileum and dog isolated middle cerebral and basilar arteries, GR203040 produced a rightward displacement of the concentration-effect curves to substance P methyl ester (SPOMe) with suppression of the maximum agonist response (apparent pKB values of 11.9, 11.2 and 11.1 respectively). 5. In anaesthetized rabbits, GR203040 antagonized reductions in carotid arterial vascular resistance evoked by SPOMe, injected via the lingual artery (DR10 (i.e. the dose producing a dose-ratio of 10) = 1.1 micrograms kg-1, i.v.). At a dose 20 fold greater than its DR10 value (i.e. 22 micrograms kg-1, i.v.), significant antagonism was evident more than 2 h after GR203040 administration. 6. In anaesthetized rats, GR203040 (3 and 10 mg kg-1, i.v.) produced a dose-dependent inhibition of plasma protein extravasation in dura mater, conjunctiva, eyelid and lip in response to electrical stimulation of the trigeminal ganglion. 7. It is concluded that GR203040 is one of the most potent and selective NK1 receptor antagonists yet described, and as such, has considerable potential as a pharmacological tool to characterize the physiological and pathological roles of substance P and NK1 receptors. GR203040 may also have potential as a novel therapeutic agent for the treatment of conditions such as migraine, emesis and pain.
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PMID:The pharmacology of GR203040, a novel, potent and selective non-peptide tachykinin NK1 receptor antagonist. 871 89

It has been suggested that murine neuroblastoma C1300 cells express endogenous neurokinin NK2 receptors with features that differ from those of NK2 receptors characterized in other systems. In this study, we have further characterized the neurokinin receptor types present in this cell line. RNA blots showed that mRNAs of NK2 and NK3 receptors, but not of NK1 receptors, were expressed in C1300 cells. The increase in the cytosolic calcium concentration ([Ca2+]i) induced by 0.33 microM neurokinin A was completely inhibited by SR 48968, an NK2 receptor antagonist, whereas the partial response to 0.33 microM neurokinin B was unaffected, and the response was completely inhibited by SR 142801, and NK3 receptor antagonist. In addition, the [Ca2+]i increase by 0.33 microM senktide, an NK3 receptor agonist, was inhibited by SR 142801 but not by SR 48968. These findings indicated that C1300 cells endogenously express functional NK2 and NK3 receptors. It was also demonstrated that NK2 and NK3 receptors can be activated independently by 3.3 microM neurokinin A in the presence of 1.0 microM SR 142801 or 1.0 microM senktide, respectively. Therefore, the mechanisms of Ca2+ signaling mediated by endogenous NK2 and NK3 receptors were investigated. The independent activation of NK2 or NK3 receptors induced not only the [Ca2+]i increase, but also stimulated the formation of inositol trisphosphates; both these responses were inhibited by U73122, a phospholipase C (PLC) inhibitor. In addition, NK2 and NK3 receptor-mediated [Ca2+]i increase was partially attenuated in the absence of extracellular Ca2+ or in the presence of nickel, an inorganic Ca2+ influx blocker, but was unaffected by nifedipine and omega-conotoxin, L- and N-type voltage-dependent Ca2+ channel blockers, respectively. Furthermore, the depolarization by 60 mM K+ did not affect the [Ca2+]i. These findings suggested that the NK2 and NK3 receptor-mediated [Ca2+]i increase was due to the activation of PLC and was dependent on the mobilization of internal Ca2+ and the entry of extracellular Ca2+ through voltage-independent channels. This study showed that the C1300 cell line is a useful system with which to investigate pharmacological functions and signaling pathways of endogenous NK2 and NK3 receptors.
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PMID:Further identification of neurokinin receptor types and mechanisms of calcium signaling evoked by neurokinins in the murine neuroblastoma C1300 cell line. 875 37

The influence of several imidazolines and sigma-site ligands on cation influx through the 5-HT3 receptor channel in N1E-115 mouse neuroblastoma cells was studied by measuring the 2-min influx of the organic cation [14C] guanidinium induced by 1 microM 5-HT (in the presence of 10 microM substance P in all experiments). In addition, we determined specific binding of [3H]DTG (1,3-di(2-tolyl)-guanidine), a selective sigma-site radioligand, and [3H] GR65630 (3-(5-methyl-1H-imidazol-4-yl)-1-(1-methyl-1H-indol-3-yl)-1- propanone), a selective 5-HT3 receptor antagonist, to membranes prepared from N1E-115 cells. The 5-HT-induced [14C]guanidinium influx was inhibited by the imidazolines, ondansetron, antazoline, idazoxan, BDF 6143 (4-chloro-2-(2-imidazolin-2-ylamino)-isoindoline), cirazoline, naphazoline, clonidine and by the guanidine agmatine, but not by the catecholamine adrenaline. The inhibitory effect of the imidazolines on cation influx through the 5-HT3 receptor channel was mimicked by the sigma-site ligands, (+/-)-ifenprodil, (+)-3-PPP ((R)-3-(3-hydroxyphenyl)-N-propylpiperidine), DTG (1,3-di-tolyl-guanidine). haloperidol, dizocilpine, and ketamine as well as by the polyamines, arcaine and spermidine.-Ondansetron inhibited [3H]GR65630 binding with high affinity, whereas inhibition of binding of this radioligand to the 5-HT3 receptor by antazoline, BDF 6143, idazoxan, cirazoline, (+/-)-ifenprodil, (+)-3-PPP, DTG and haloperidol occurred in the high micromolar range. In the competition experiments with [3H]DTG, (+/-)-ifenprodil, haloperidol, unlabelled DTG, BDF 6143 and (+)-3-PPP inhibited binding of the radioligand at moderate affinity (Ki values in the range of 1 microM or lower), whereas ondansetron, antazoline, idazoxan, cirazoline, naphazoline, clonidine, tolazoline, efaroxan, RX821002 (2-[2-(2-methoxy-1,4-benzodioxanyl)]imidazoline), ketamine and spermidine exhibited affinity, in the high micromolar or millimolar range only. Comparison of the potencies of the ligands (pIC50% values) in inhibiting 5-HT-induced [14C]guanidinium influx with their affinities (pKi values) at the 5-HT recognition sites of the 5-HT3 receptor and at the sigma 2-sites of the N1E-115 cells by means of multiple regression analysis revealed a significant correlation with the affinities at both sites. In conclusion, our data suggest that imidazolines and sigma-ligands, which as a rule possess low affinity for the 5-HT recognition site of the 5-HT3 receptor, may be assumed to exert their inhibitory effect on cation influx through the 5-HT3 receptor channels, at least in part, by interacting with sigma 2-binding sites.
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PMID:Inhibition of 5-HT3 receptor function by imidazolines in mouse neuroblastoma cells: potential involvement of sigma 2 binding sites. 887 53

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