UMLS:C0043167 - FACTA Search

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Query: UMLS:C0043167 (pertussis)
19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ligand-induced up-regulation of recombinant dopamine D2 receptors was assessed using C6 glioma cells stably expressing the short (415-amino-acid; D2s) and long (444-amino-acid; D2L) forms of the receptor. Overnight treatment of C6-D2L cells with N-propylnorapomorphine (NPA) caused a time- and concentration-dependent increase in the density of receptors, as assessed by the binding of radioligand to membranes prepared from the cells, with no change in the affinity of the receptors for the radioligand. The effect of 10 microM NPA was maximal after 10 h, at which time the density of D2L receptors was more than doubled. The agonists dopamine and quinpirole also increased the density of D2L receptors. The receptor up-regulation was not specific for agonists, because the antagonists epidepride, sulpiride, and domperidone caused smaller (30-60%) increases in receptor density. Prolonged treatment with 10 microM NPA desensitized D2L receptors, as evidenced by a reduced ability of dopamine to inhibit adenylyl cyclase, whereas treatment with sulpiride was associated with an enhanced responsiveness to dopamine. The magnitude of NPA-induced receptor up-regulation in each of four clonal lines of C6-D2L cells (mean increase, 80%) was greater than in all four lines of C6-D2S cells (33%). Inactivation of pertussis toxin-sensitive G proteins had no effect on the basal density of D2L receptors or on the NPA-induced receptor up-regulation. Treatment with 5 micrograms/ml of cycloheximide, on the other hand, decreased the basal density of receptors and attenuated, but did not prevent, the NPA-induced increase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Drug-induced up-regulation of dopamine D2 receptors on cultured cells. 761 11

1. The effects of chronic in vitro administration of amitriptyline, a tricyclic antidepressant, on 5-hydroxytryptamine (5-HT) receptor-mediated adenylyl cyclase activity was studied in the neuroblastoma x glioma hybrid cell line, NG 108-15. 2. Treatment of NG 108-15 cells with 8 microM amitriptyline for 3 days increased forskolin-stimulated (0.1 microM) adenosine 3':5'-cyclic monophosphate (cyclic AMP) accumulation. Addition of 5-HT (0.1-100 microM) increased forskolin-stimulated cyclic AMP accumulation in amitriptyline-treated cells in a concentration-dependent manner. However, 5-HT did not affect forskolin-stimulated cyclic AMP accumulation in untreated cells. 3. The 5-HT4 receptor agonist, 5-methoxytryptamine, significantly enhanced forskolin-stimulated cyclic AMP accumulation in amitriptyline-treated cells. In contrast, amitriptyline treatment failed to modify 8-hydroxy-2-(di-n-propylamine) tetralin-induced inhibition of forskolin-stimulated cyclic AMP accumulation. 4. Pretreatment of cells with pertussis toxin did not affect the 5-HT-induced enhancement of cyclic AMP accumulation. 5. The 5-HT-induced enhancement of cyclic AMP accumulation in amitriptyline-treated cells was attenuated by the 5-HT4 receptor antagonists, GR 113808 and ICS 205-930, with relatively low potency. However, spiperone, SCH 23390, and pindolol were completely ineffective against this 5-HT-induced enhancement. 6. Chronic treatment with amitriptyline did not modify the cyclic AMP production stimulated by prostaglandin E1 or cholera toxin. This treatment also had no effect on GTP gamma S-, NaF-, and Mn(2+)-stimulated cyclic AMP accumulation in isolated cell membranes. 7. Chronic treatment with the 5-HT receptor antagonists, pindolol or ICS 205-930, did not inhibit the 5-HT-induced enhancement of cyclic AMP accumulation.8. Chronic treatment with other antidepressant drugs, imipramine, mianserin or paroxetine, elicited the 5-HT-induced enhancement of cyclic AMP accumulation.9. Taken together, these results suggest that chronic amitriptyline treatment of NG 108-15 cells causes 5-HT to enhance forskolin-stimulated cyclic AMP accumulation by enhancing 5-HT receptor-mediated stimulation of adenylyl cyclase and not by reducing 5-HT-mediated inhibition of adenylyl cyclase. The 5-HT-induced enhancement of cyclic AMP accumulation in amitriptyline-treated cells may result from changes at the level of the 5-HT receptor rather than at the level of G, proteins or adenylyl cyclase. It is unlikely that this enhancement of cyclic AMP accumulation is caused by long-term antagonism of the 5-HT receptor by amitriptyline.
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PMID:Enhancement of cyclic AMP accumulation mediated by 5-HT after chronic amitriptyline treatment in NG 108-15 cells. 762 Jul 19

Voltage-dependent Ca2+ currents were measured in NG108-15 neuroblastoma x glioma hybrid cells transformed to express the rat mu-opioid receptor by the whole-cell configuration of the patch-clamp technique with Ba2+ as charge carrier. A mu-opioid receptor-selective agonist, [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin caused significant inhibition of voltage-dependent Ca2+ currents in mu-receptor-transformed NG108-15 cells but not in nontransfected or vector-transformed control cells. On the other hand, a delta-opioid receptor-selective agonist, [D-penicillamine2,D-penicillamine5]enkephalin, induced inhibition of voltage-dependent Ca2+ currents in both control and mu-receptor-transformed cells, which is mediated by the delta-opioid receptor expressed endogenously in NG108-15 cells. The inhibition of voltage-dependent Ca2+ currents induced by [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin [D-penicillamine2,D-penicillamine5]enkephalin was reduced by pretreatment of the cells with pertussis toxin or omega-contoxin GVIA. These results indicate that the mu-opioid receptor expressed from cDNA functionally couples with omega-contoxin-sensitive N-type Ca2+ channels through the action of pertussis toxin-sensitive G proteins in NG108-15 cells.
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PMID:Coupling of the cloned mu-opioid receptor with the omega-conotoxin-sensitive Ca2+ current in NG108-15 cells. 764 19

Neuroblastoma NS20Y cells possess a high density of stereoselective delta opioid receptors as determined by competition binding with 3H-diprenorphine and various opioid ligands. Scatchard analysis of [3H]diprenorphine saturation binding data revealed a Kd = 0.79 +/- 0.17 nM and Bmax = 370 +/- 50 fmol/mg protein. These opioid binding sites have highest affinity for delta opioid receptor selective agonists and lowest affinity for mu opioid receptor selective agonists. Agonist binding was sensitive to the presence of the monovalent cation, Na+. Activation of receptor with D-Ala2, D-Leu5-enkephalin (DADLE) resulted in dose-dependent inhibition of forskolin-stimulated intracellular [3H]cAMP accumulation, which was antagonized by (-)-naloxone but not (+)-naloxone. Relative potencies of various opioid agonists to inhibit intracellular cAMP production paralleled those observed in neuroblastoma x glioma NG108-15 hybrid cells. Pretreatment of NS20Y cells with pertussis toxin (PTX) eliminated opioid agonist inhibition of adenylyl cyclase activity. Chronic DADLE treatment resulted in desensitization and down-regulation of opioid receptor. An increase in intracellular [3H]cAMP level above the control was observed in the presence of naloxone after chronic DADLE treatment. Therefore, opioid binding sites in neuroblastoma NS20Y cells possess properties of the classical delta opioid receptor type. After neuroblastoma NS20Y was growth arrested by culturing the cells in serum-free medium for 72 hr, proliferation was reinitiated by addition of fetal calf serum (FCS), 0.01% to 12%, and was monitored by either [3H]thymidine incorporation or by dye viability assay. It was demonstrated that naloxone and naltriben but not Met5-enkephalin could attenuate FCS-induced proliferation in a dose-dependent manner. Naltriben was 54-fold more potent than naloxone to attenuate NS20Y proliferation. The maximal level of viable cells per well was reduced (35.2 +/- 1.9%) with no alteration in FCS concentration-dependent stimulation of growth. Similar inhibition by naloxone (37.3 +/- 2.7%) was observed with [3H]thymidine incorporation studies. This naloxone effect was serum concentration-dependent and could be blocked by culturing NS20Y cells in the presence of both naloxone and Met5-enkephalin. Although pretreatment of NS20Y cells with pertussis toxin could attenuate FCS-stimulated proliferation, naloxone effect on growth was not affected by pertussis toxin pretreatment. Furthermore, the naloxone effect was not NS20Y specific. A similar naloxone effect was observed with neuroblastoma N1E115, although not with neuroblastoma x glioma NG108-15, nor human neuroblastoma SHSY5Y, cell lines that have been reported to contain delta opioid receptors. Therefore, activation of delta opioid receptor could modulate FCS-induced growth in some but not all neuroblastoma cell lines.
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PMID:Properties of delta opioid receptor in neuroblastoma NS20Y: receptor activation and neuroblastoma proliferation. 781 47

A phospholipase-C-linked nucleotide receptor, sensitive to both uridine and adenosine triphosphate (UTP and ATP) has been cloned from NG108-15 neuroblastoma x glioma hybrid cells. We have tested whether activation of this receptor could inhibit the voltage-dependent K+ current [IK(M) or "M-current"] in NG108-15 cells recorded using whole-cell patch-clamp methods. Both UTP and ATP inhibited IK(M) by 44% and 42%, respectively, at 100 microM. Mean IC50 values were: UTP, 0.77 +/- 0.27 microM; ATP, 1.81 +/- 0.82 microM. The order of nucleotide and nucleoside activity at 100 microM was: UTP = ATP > ATP [gamma S] = ITP > 2-MeSATP > ADP = GTP >> AMP-CPP, adenosine, where ATP[gamma S] is adenosine 5'-O-(3-thiotriphosphate), ITP is inosine 5'-triphosphate, 2-MeSATP is 2-methylthio ATP and AMP-CPP is alpha, beta methylene ATP. This rank order accords with their activities at the cloned P2U receptor. Effects were not inhibited by suramin (up to 500 microM) or by pre-incubation for 12 h in 500 ng.ml-1 Pertussis toxin. Inhibition of IK(M) was frequently preceded by a transient outward current, probably a Ca(2+)-activated K+ current, responding to Ca2+ mobilization. No effect on the delayed rectifier K+ current was observed. These observations match those expected from stimulating other phospholipase-C-linked receptors in NG108-15 cells.
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PMID:Activation of nucleotide receptors inhibits M-type K current [IK(M)] in neuroblastoma x glioma hybrid cells. 789 8

This study describes the depression of calcium currents caused by activation of human D3 dopamine receptors which have been stably expressed in the neuroblastoma x glioma NG108-15 cell line. Transfected cells, which had been differentiated with prostaglandin E1 and isobutylmethylxanthine, exclusively expressed D3 receptor mRNA, which was demonstrated by reverse transcription polymerase chain reaction techniques. Transfected cells had high affinity binding sites for iodosulpiride, with a Kd of 0.8 nM and receptor density of 240 fmol mg-1 protein. Calcium currents were recorded using nystatin-perforated patch clamp techniques. In contrast to untransfected cells that had been differentiated, high-threshold calcium currents in differentiated hD3-NG108-15 cells were depressed by application of dopamine and quinpirole. These responses were abolished by the dopamine receptor antagonist S-(-)-sulpiride (1 microM), demonstrating that they were caused by the activation of the transfected dopamine receptors. Coupling of human D3 receptors to calcium currents was sensitive to the action of pertussis toxin, suggesting the involvement of G-proteins of the Gi and/or G(o) subtype. These results demonstrate that human D3 receptors represent a functional class of dopamine receptor.
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PMID:Functional expression of human D3 dopamine receptors in differentiated neuroblastoma x glioma NG108-15 cells. 791 12

Opioid agonists inhibit DNA synthesis in C6 rat glioma cells that express opioid receptors, induced by desipramine (DMI). This inhibition was not observed in cells that were not treated with DMI, and thus did not express opioid-binding sites. Endothelin, a known mitogen, increased thymidine incorporation dose dependently (up to 1.7-fold) in DMI-treated C6 cells. This increase was reversed by an anti-idiotypic antibody to opioid receptors, Ab2AOR, which has opioid agonist properties. The opioid antagonist naltrexone blocked the inhibition caused by Ab2AOR. Endothelin also stimulated phosphoinositide (PI) turnover and this effect was inhibited by morphine (50%) or by Ab2AOR (72%) in DMI-treated but not in DMI-untreated C6 cells. These actions of morphine and Ab2AOR were reversed by naltrexone. The inhibition of PI turnover and of thymidine incorporation by Ab2AOR or morphine was insensitive to pertussis toxin (PTX). Since PI turnover is known to induce Ca2+ mobilization, it was of interest to examine the effects of the applied opioids on intracellular Ca2+ concentrations. Endothelin increased the concentration of cytosolic free Ca2+ in the cells while Ab2AOR, morphine, and beta-endorphin reversed the endothelin-induced Ca2+ mobilization in DMI-treated but not in DMI-untreated C6 cells. The effect of these agonists was also blocked by naltrexone. The results indicate that glial cells can be a target of an opioid receptor-mediated antimitogenic action and that an abatement in PI turnover and Ca2+ mobilization may be associated with this mechanism.
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PMID:Opioids inhibit endothelin-mediated DNA synthesis, phosphoinositide turnover, and Ca2+ mobilization in rat C6 glioma cells. 793 48

In neuroblastoma-glioma hybrid cells, bradykinin has dual modulatory effects on ion channels: it activates a K+ current as well as inhibits the voltage-dependent Ca2+ current (ICa,V). Both of these actions are mediated by pertussis toxin-insensitive G proteins. Antibodies raised against the homologous Gq and G11 proteins suppress only the activation of the K+ current; this suggested that at least two distinct G protein pathways transduce diverse effects of this transmitter. Here, we show that the inhibition of ICa,V by bradykinin is suppressed selectively by intracellular application of antibodies specific for G13. This novel G protein may play a general role in the inhibition of ICa,V by pathways resistant to pertussis toxin.
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PMID:The G protein G13 mediates inhibition of voltage-dependent calcium current by bradykinin. 794 58

Transfection of a human dopamine D3 receptor cDNA in a neuroblastoma-glioma hybrid cell line (NG 108-15) provided clonal cell lines stably expressing up to 600 fmol per mg protein of [125I]iodosulpiride binding sites. Dopamine and several agonists distinguished two receptor-affinity states in membranes. In the case of dopamine, the high-affinity state (Ki = 0.9 nM, 30% of total binding) was completely converted into a low-affinity state (Ki = 57 nM) in the presence of 10 microM guanosine-5'-O-(3-thiotriphosphate). In addition to these two sites, a site with a very low affinity for dopamine was evidenced in whole cells. The dopamine D3 receptor mediated two responses: c-fos activation, as measured by the appearance of Fos-like immunoreactivity, and increased mitogenesis, as measured by incorporation of [3H]thymidine. The Fos-like immunoreactivity appeared within 30 min, lasted 2 h and was blocked by the partially selective dopamine D3 receptor compound (+)-UH 232 (cis-(+)-5-methoxy-1-methyl-2-(di-n-propylamino)tetralin). The mitogenic effect, which occurred after a lag time (over 2 h stimulation), was produced with subnanomolar potency and full intrinsic activity by several compounds previously identified as dopamine D2 receptor agonists, e.g. quinpirole, (+)-7-OH-DPAT ((+)-7-hydroxy-2-(di-n-propylamino)tetralin) and RU 24926 (N-n-propyl-di-beta(3-hydroxyphenyl)-ethylamine), and was reversibly blocked by (+)-UH 232 (Ki = 9 nM). Talipexole (B-HT 920, 5-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo[4,5-d]azepin) was identified as a partial agonist at the dopamine D3 receptor. Dopamine D3 receptor-mediated mitogenesis was potentiated by a phorbol ester and was abolished by pretreatment with pertussis toxin. A mitogenic effect of same amplitude was elicited by bradykinin or carbachol, both acting through constitutive receptors. Bradykinin markedly activated inositol phosphate turnover, and had no effect on forskolin-stimulated cyclic AMP accumulation. Carbachol inhibited forskolin-stimulated cyclic AMP accumulation and had no effect on inositol-phosphate turnover. Quinpirole had no effect on any of these second messenger pathways. Thus, in transfected NG 108-15 cells, the dopamine D3 receptor is coupled to a pertussis toxin-sensitive G protein and mediates two possibly unrelated biological effects, through initial biochemical events that remain to be identified.
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PMID:Functional coupling of the human dopamine D3 receptor in a transfected NG 108-15 neuroblastoma-glioma hybrid cell line. 795 35

In C6 glioma cells, extracellular ATP and other nucleotide analogs stimulated phosphoinositide (PI) breakdown and inhibited isoproterenol-induced cyclic AMP (cAMP) accumulation. The rank orders of potencies of 15 nucleotide analogs for both responses were clearly different. ATP and adenosine 5'-O-(3-thiotriphosphate) are the most potent agonists for stimulating PI hydrolysis; 2-methylthio-ATP (2-MeSATP) is the most potent agonist for inhibiting cAMP accumulation. P1-mediated responses of PI turnover and cAMP formation are not present in C6 glioma cells. Pertussis toxin (PTX) blocked the nucleotide-induced inhibition of cAMP accumulation but exerted no effect on inositol phosphate formation. Short-term treatment with phorbol 12-myristate 13-acetate inhibited both signal transduction pathways. The effects of three P2 purinergic antagonists, suramin, reactive blue and 4,4'-diisothiocyanatostilbene sulfonic acid (DIDS), on ATP- and 2-MeSATP-induced stimulation of PI turnover and inhibition of cAMP formation, respectively, were compared. For stimulating PI turnover, suramin is a competitive antagonist (pA2, 4.4); reactive blue and DIDS are noncompetitive antagonists at 30 microM and 100 microM, respectively. For the inhibition of cAMP formation, reactive blue and DIDS competitively antagonized the response of 2-MeSATP (pA2 values, 6.3 for reactive blue and 5.7 for DIDS); suramin was only slightly effective at 100 microM. It was concluded that the nucleotide receptor is linked to phospholipase C by a PTX-insensitive Gp protein and the P2Y receptor is linked to adenylyl cyclase by a PTX-sensitive Gi protein. Suramin is a competitive antagonist for the nucleotide receptor; reactive blue and DIDS are more selective antagonists for the P2Y receptor.
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PMID:Different signal transduction pathways are coupled to the nucleotide receptor and the P2Y receptor in C6 glioma cells. 801 79

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