Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The nature of the leukotriene-D4 (LTD4) induced cell shrinkage in Ehrlich ascites tumor cells has been investigated. LTD4 treatment of Ehrlich cells induces net loss of cellular KCl and cell shrinkage independent of the initial cell volume. LTD4 also produces water loss and reduction in cell volume when all extracellular and all intracellular Cl has been replaced by NO3. On the other hand, LTD4 fails to produce any significant changes in cell volume in the presence of the K-channel blocker quinine, suggesting that LTD4 in Ehrlich cells induces Cl-independent K loss through the Ca2+-dependent K channels. However, the effect of physiological doses of LTD4 on cell volume seems not to be as potent in Cl-free, NO3 cells when compared to Cl-containing cells, indicating that LTD4 in Ehrlich cells also provokes Cl-dependent K loss. LTD4 seems not to produce K loss through an electroneutral K+/H+ exchange system. LTD4 still produces Cl-independent K loss and cell shrinkage in the presence of the anti-calmodulin drug pimozide but not in the presence of the LTD4 receptor antagonist L-649,923 or the 5-lipoxygenase inhibitor NDGA. Pretreatment of the cells with pertussis toxin, which inactivates inhibitory guanine nucleotide binding proteins (G-proteins), leads to partial inhibition of the LTD4-induced shrinkage. It is suggested that the LTD4-induced activation of K and Cl transporting systems in Ehrlich ascites tumor cells is mediated via a G-protein coupled receptor and that LTD4 might exert its effect through another lipoxygenase product. The Ca2+-calmodulin complex is not involved in the LTD4-induced activation of K and Cl transporting systems.
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PMID:Leukotriene-D4 induced cell shrinkage in Ehrlich ascites tumor cells. 247 62

Endothelin-1 (ET-1) and parathyroid hormone (PTH) increase calcium transients in rodent osteoblastic cells. To investigate the role of phospholipase C (PLC) in these hormone-stimulated calcium signals, the effects of U-73122 (1-[6-[[17 beta-3-methoxyestra-1,3,5(10)- trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione), a reported PLC inhibitor, and its inactive analog, U-73343 (1-[6[[17 beta-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]- 1H-pyrrolidine-2,5-dione), were determined. Intracellular calcium transients were measured in UMR-106 cells with the fluorescent indicator fluo-3. In normal calcium containing medium, prior exposure (3 min) to U-73122 inhibited ET-1 and PTH stimulated calcium transients in a dose-dependent (0.2-10 microM) manner with an IC50 of 1.5-1.8 microM. A concentration of 6-8 microM was required for complete inhibition of responses to 100 nM ET-1 or PTH. U-73343 elicited no effects over this concentration range. In cells in which external calcium was reduced to less than 1 microM by the addition of EGTA, ET-1 signals were completely inhibited by 4-6 microM U-73122 and the IC50 was 0.8 microM. In the low external calcium medium, the PTH response was abolished by 2 microM U-73122 (IC50 = 0.5 microM). U-73122, 8 microM, significantly (P < 0.01) inhibited the effect of ET-1 on inositol trisphosphate production at 3 min whereas U-73343 did not. Pertussis toxin (100 ng/ml) likewise significantly inhibited the effect of ET-1 on phosphoinositol turnover as well as on intracellular calcium concentration. In conclusion, the results support the hypothesis that PLC plays a role in the calcium transients elicited by ET-1 and PTH, and that ET-1 transmits its signal in part via a pertussis toxin sensitive G-protein coupled receptor. Furthermore they suggest that U-73122 is useful for investigating PLC-mediated process in osteoblastic cells.
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PMID:U-73122, a phospholipase C antagonist, inhibits effects of endothelin-1 and parathyroid hormone on signal transduction in UMR-106 osteoblastic cells. 780 18

Peptides which stimulate the formation of inositol phosphates (InoPs) in lymphocyte cell lines were identified by screening synthetic peptide libraries composed of random sequences of hexapeptides. The peptides containing the consensus sequence XKYX(P/V)M were found to be most active in the phospholipase C (PLC)-mediated formation of InoPs in a human B myeloma cell line, U266. The peptides also stimulated the phosphoinositide hydrolysis and the release of [Ca2+]i in HL60 and U937 cell lines. On the other hand, these peptides showed no effect in the following cell lines: NIH3T3, PC12, Daudi, Sp2, Jurkat, H9, Molt-4, SupT-1, K562, and RBL-2H3. The result suggests the possibility that the peptides may have cell type specificity. Experiments with one of the active peptides, WKYMVM-NH2 showed that its action mimics the effect of AlF4- which is a G-protein activator in the InoPs generation, and pertussis toxin partially blocked the InoPs accumulation and [Ca2+]i release induced by the peptide in the U266 cells. Binding assays with the peptide labeled with 125I showed that U266 cells have a saturable number of binding sites for the peptide. Taken together, these results suggest that the peptides could activate PLC-mediated signal transduction via a pertussis toxin-sensitive G-protein coupled receptor in certain cell types.
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PMID:Identification of the peptides that stimulate the phosphoinositide hydrolysis in lymphocyte cell lines from peptide libraries. 862 7

Mammalian bombesin-like peptides gastrin-releasing peptide (GRP) and neuromedin B (NMB) are regulatory neuropeptides involved in numerous physiologic processes, and have been implicated as autocrine and/or paracrine growth factors in human lung carcinoma. Three structurally and pharmacologically distinct bombesin receptor subtypes have been isolated and characterized: the gastrin releasing peptide receptor (GRP-R), the neuromedin B receptor (NMB-R), and bombesin receptor subtype-3 (BRS-3). The three receptors are structurally related, sharing about 50% amino acid identity. They are members of the G-protein coupled receptor superfamily with a seven predicted transmembrane segment topology characteristic of receptors in this family. The signal transduction pathway for GRP-R and NMB-R involves coupling to a pertussis-toxin insensitive G-protein, activation of phospholipase C (PLC), generation of inositol trisphosphate (IP3), release of intracellular calcium, and activation of protein kinase C. While all three bombesin receptors are activated by bombesin agonists, GRP-R, NMB-R, and BRS-3 have very different affinities for the mammalian bombesin-like peptides GRP and NMB, as well as bombesin receptor antagonists. The three bombesin receptor subtypes are expressed in an overlapping subset of human lung carcinoma cell lines. Any therapeutic strategy based on modulation of bombesin growth responses in human lung carcinoma would be well served to take into account the pharmacologic heterogeneity of the relevant receptors.
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PMID:Bombesin receptor structure and expression in human lung carcinoma cell lines. 880 6

The chicken pineal gland has an endogenous circadian oscillator that controls the diurnal oscillation of N-acetyltransferase activity responsible for melatonin rhythm. It has been speculated that the chicken pineal cell contains a photoreceptive molecule that receives the environmental light signal and transmits the signal to the oscillator for resetting the phase. In spite of several lines of evidence suggesting the similarity between retinal and pineal photon-signal transducing proteins, the identity of the photoreceptive molecule had been an open question. In 1994, we isolated a pineal cDNA encoding a novel photoreceptive molecule and named it "pinopsin." The protein expressed in 293EBNA cells bound 11-cis-retinal to form a blue-sensitive pigment with an absorption maximum at about 470 nm. A putative G-protein interaction site of pinopsin shared a relatively high similarity in amino acid sequence to that of rhodopsin, implying that pinopsin functionally couples with transducin or transducin-like G-protein(s) in the pineal cells. We have cloned a cDNA for chicken pineal transducin alpha-subunit, and the deduced amino acid sequence contained a potential site to be ADP-ribosylated by pertussis toxin (PTX). Therefore, the transducin-mediated pathway could be blocked by PTX, though previous studies showed that treatment of the cultured chicken pineal cells with PTX had no effect on the light-induced phase-shift of the oscillator. Accordingly, it is unlikely that transducin mediates the light-input pathway to the oscillator, which may involve PTX-insensitive G-protein(s) or some unidentified component(s). The G-protein coupled receptor-mediated signaling processes regulating melatonin synthesis are discussed.
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PMID:Phototransduction cascade and circadian oscillator in chicken pineal gland. 921 68

Prostaglandins, produced in response to mitogens and cytokines, are potent modulators of gastrointestinal physiology and pathophysiology. We investigated modulation of Prostaglandin synthase 2 (PGS-2) expression by the gastrin-releasing peptide (GRP) receptor in Swiss 3T3 cells. PGS-2 mRNA expression in Swiss 3T3 cells was determined by Northern blot analysis. PGS-2 protein expression in Swiss 3T3 cells was measured by Western blot analysis. GRP caused a transient induction of PGS-2 mRNA in Swiss 3T3 cells that resulted in GRP-dependent expression of PGS-2 protein. Transcriptional activation of PGS-2 by GRP was independent of de novo protein synthesis and was not affected by pertussis toxin. Comparison of signaling pathways used by PMA or EGF to those used by GRP showed that PGS-2 induction by GRP increased under conditions that inhibit PKC activity. Dexamethasone, which blocks PMA and EGF induction of PGS-2, also inhibited GRP-induced accumulation of PGS-2 mRNA. These results show that PGS-2 expression in Swiss 3T3 cells is not only controlled by PKC and receptor tyrosine kinase pathways but also by G-protein coupled receptor signaling pathways.
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PMID:Gastrin-releasing peptide-induced expression of prostaglandin synthase-2 in Swiss 3T3 cells. 949 Dec 6

Sphingosine 1-phosphate (SphP), a metabolite of cellular sphingolipids, has been shown to induce cell proliferation by activating the mitogen-activated protein kinase (MAPK) pathway. Proline-rich tyrosine kinase 2 (Pyk2) is a novel cytosolic tyrosine kinase which mediates activation of the MAPK or c-Jun N-terminal kinase (JNK) signaling pathways in response to a variety of stimuli that elevate intracellular calcium. In this report, we show that SphP stimulates both tyrosine phosphorylation of Pyk2 and MAPK activation in a transient and dose-dependent manner in rat aortic smooth muscle cells. Further studies indicate that Pyk2 phosphorylation, but not MAPK activation, is dependent on a pertussis toxin-sensitive G-protein-coupled receptor as well as partially on actin cytoskeleton. In addition, both intracellular calcium mobilization and protein kinase C (PKC) are required for optimal Pyk2 phosphorylation while either calcium increase or PKC activation is sufficient for MAPK activation in response to SphP. Finally, we show that a tyrosine kinase(s) other than Pyk2 is necessary for MAPK activation by SphP. Together, these results suggest that SphP stimulates tyrosine phosphorylation of Pyk2 through a G-protein coupled receptor, which is dissociated from its activation of the MAPK pathway in these cells.
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PMID:Differential stimulation of proline-rich tyrosine kinase 2 and mitogen-activated protein kinase by sphingosine 1-phosphate. 982 86

Fusion proteins between the human A(1) adenosine receptor and the pertussis toxin resistant (Cys351Gly) mutant of the G-protein alpha subunit G(i1)alpha (A1/Gi), and between the human A(1) adenosine receptor, the Aequorea victoria green fluorescent protein (GFP) and Cys351Gly G(i1)alpha (A1/GFP/Gi), were expressed in CHO cells. The agonist NECA caused a stimulation of [(35)S]GTPgammaS binding at both fusion proteins with similar concentration dependence as at the native receptor. However in the presence of pertussis toxin NECA stimulation of [(35)S]GTPgammaS binding was only seen at the A1/GFP/Gi fusion protein. The regulation of the adenylyl cyclase and MAP kinase effector systems by both fusion proteins was attenuated following pertussis toxin treatment. These studies demonstrate for the first time the characterisation of a fusion protein between a G-protein coupled receptor, GFP and a G-protein alpha subunit.
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PMID:Functional analysis of a human A(1) adenosine receptor/green fluorescent protein/G(i1)alpha fusion protein following stable expression in CHO cells. 1058 92

A retro-inverso 11-mer peptidomimetic of prosaposin, Prosaptide D5, induced neurite outgrowth in NS20Y neuroblastoma cells and enhanced [35S]GTPgammaS binding to rat synaptosomal membrane at low nanomolar concentrations similar to prosaposin. Intramuscular injection of D5 ameliorated thermal hyperalgesia in the Seltzer rat model of neuropathic pain, returning paw withdrawal latency to control levels within 3 h after treatment. The effect was sustained for at least 48 h after injection. Prosaposin and D5 inhibited K+-stimulated synaptosomal 45Ca2+ uptake similar to omega-conotoxin MVIIC, demonstrating that both effectors modulated voltage-dependent calcium channels (VDCC); inhibition was largely abolished by pretreatment with pertussis toxin before D5 treatment. The results suggest a mechanism whereby VDCC are modulated by a pertussis toxin-sensitive G-protein coupled receptor; D5 binds to this receptor and thereby ameliorates hyperalgesia in the Seltzer model of neuropathic pain.
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PMID:Prosaptide D5 reverses hyperalgesia: inhibition of calcium channels through a pertussis toxin-sensitive G-protein mechanism in the rat. 1064 16

We present evidence of a link between low-density lipoprotein (LDL) receptor binding and activation of a platelet G-coupled protein. LDL stimulation induced cytosolic [Ca2+]i mobilization, increase in inositol 1,4,5-triphosphate (IP3) formation and a rapid cytosol-to-membrane translocation of protein kinase C (PKC) enzymatic activity. Pertussis toxin inhibited all the stimulatory effects, whereas cholera toxin had no effect. Using ligand-binding assays, we demonstrated that exposing platelet LDL receptors to high concentrations of LDL (1.5 g/l) caused a rapid down-regulation and desensitization, as shown by the reduction in the Bmax, intracellular [Ca2+]i mobilization and IP3 formation to 65, 73 and 63%, respectively. The inhibitory effects were reversible and dose and time dependent. Furthermore, VLDL (0.2 g/l) and IDL (0.07 g/l) induced similar desensitization effects. However, HDL3 (up to 1.5 g/l), chylomicrons (up to 0.5 g/l) and cyclohexandione-modified LDL (which does not bind to platelets) had no significant effects. Protein kinase C inhibitors (150 nmol/l staurosporine, 100 micromol/l H-7, and 10 nmol/l bisindolylmaleimide) inhibited desensitization to 71%, on average. Sequestration blocking agents (0.30 g/l, concanavalin A) had no significant effect if phosphorylation was operative. However, there was a complete blockade with the concurrent inhibition of both pathways. In contrast, cAMP-dependent protein kinase inhibitors (PKI, 1 micromol/l) or beta2-adrenergic receptor kinase inhibitors (100 nmol/l, heparin), had no effect. Overall results indicate that LDL binds to a pertussis sensitive G-protein coupled receptor and that high levels of lipoproteins down-regulate the number of receptors and desensitize its mediated response by a mechanism that involves PKC-phosphorylation and sequestration of binding sites. This new regulatory mechanism may have implications for the thrombogenicity in hyperlipidemia and for effects of lipid lowering therapy.
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PMID:Low-density lipoprotein (LDL) binds to a G-protein coupled receptor in human platelets. Evidence that the proaggregatory effect induced by LDL is modulated by down-regulation of binding sites and desensitization of its mediated signaling. 1122 31


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