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)

The properties of phospholipase C (PL-C) in the plasma membranes (PM) and the cytosol of osteoblast-like osteosarcoma cells, UMR-106, were analyzed to see if separate enzymes or similar enzymes were involved in signalling, transduction, and arachidonate release. The cytosolic PL-C displayed substrate affinities in the order of phosphatidylinositol (PI) greater than phosphatidylinositol-4-phosphate (PIP) or phosphatidylinoisitol-4, 5-bisphosphate (PIP2). Hydrolysis of PI, PIP, and PIP2 by cytosolic PL-C was not affected by GTP or GTP gamma S and other nucleotides. PI hydrolysis by PM and cytosolic PL-C was undetectable in the presence of 500 microM EGTA and displayed two activity plateaus at various concentrations of Ca2+. The Km for Ca2+ in the PL-C activity of the first plateau was 0.08 microM. Significant hydrolysis of PIP2 by cytosolic PL-C was observed in the absence of Ca2+. In contrast to the enzyme(s) predominant in the cytosol, the order of substrate affinities for PM PL-C was PIP2 greater than PIP greater than PI. Only PIP2 hydrolysis by PM PL-C was stimulated by both GTP and GTP gamma S in a dose-dependent manner. PIP2 hydrolysis by PL-C of the PM was not observed in the absence of Ca2+, serving to further discriminate this enzyme activity from that of the cytosol. PIP2 hydrolysis by PL-C of the PM also was biphasic in the dependence on Ca2+. At resting cytosolic Ca2+ levels, the Vmax of the high affinity activity already had been achieved. Guanine nucleotide stimulation of PIP2 hydrolysis by PM PL-C was characterized by increased maximum activity with an unchanged Km for Ca2+ or for PIP2. The pH optimum of PIP2 hydrolysis was similar between cytosolic and PM forms of PL-C. PIP2 hydrolysis with production of IP3 (PL-C activity) in UMR-106 cells treated with [2-3H]-myoinositol was stimulated by PTH, and this stimulation was not inhibited by pertussis toxin. These data suggest that UMR-106 cells possess at least two distinct PL-C activities, one predominant in the cytosol and activated by increasing cytosolic Ca2+ with PI as the substrate. The second enzyme, a GTP-activated PIP2-specific PL-C in the plasma membranes may play an important role in hormone-induced PIP2 hydrolysis mediated through guanine nucleotide regulatory proteins and may participate in the hormonal regulation of osteoblast cytosolic Ca2+ and bone remodeling functions.
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PMID:Characterization of phospholipase C activity of the plasma membrane and cytosol of an osteoblast-like cell line. 292 33

Treatment of membranes from bovine cerebral cortex with N-ethylmaleimide (NEM) resulted in inhibition of gamma-aminobutyric acid (GABA) binding to GABAB receptors. The binding curve for increasing concentrations of agonist was shifted to the right by NEM treatment. Guanine nucleotide had little effect on the binding of GABA to NEM-treated membranes. The addition of purified GTP-binding proteins, which were the substrates of islet-activating protein (IAP), pertussis toxin, to the NEM-treated membranes caused a shift of the binding curve to the left, suggesting modification of GTP-binding proteins rather than receptors by NEM. Therefore, the effect of NEM on two purified GTP-binding proteins, Gi (composed of three subunits with molecular weight of alpha, 41,000; beta, 35,000; gamma, 10,000) and Go (alpha, 39,000; beta, 35,000; gamma, 10,000) was studied. NEM did not significantly change guanosine 5'-(3-O-thio)triphosphate (GTP gamma S) binding and GTPase activity of these two proteins. In contrast, NEM-treated Gi and Go were not ADP-ribosylated by IAP and did not increase GABA binding to NEM-treated membranes. When alpha and beta gamma subunits were treated with NEM and then mixed with nontreated alpha and beta gamma to form Gi or Go, respectively, both oligomers with NEM-treated alpha-subunits lost their abilities to be IAP substrates and to couple to receptors. These results indicate that NEM uncoupled GTP-binding proteins from receptors by modifying alpha-subunits of GTP-binding proteins, and the site seemed to be on or near the site of ADP-ribosylation by IAP. When alpha and beta gamma subunits were treated with NEM and then mixed to form Gi or Go, GTP gamma S binding in the absence of Mg2+ and GTPase activity were changed, although they were not affected when oligomers were treated with NEM. The results suggest the existence of another sulfhydryl group which is protected from NEM by the association of subunits. The modification of this sulfhydryl group by NEM appeared to interfere with the interaction between alpha and beta gamma.
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PMID:Uncoupling of gamma-aminobutyric acid B receptors from GTP-binding proteins by N-ethylmaleimide: effect of N-ethylmaleimide on purified GTP-binding proteins. 300 32

Guanine nucleotide-binding regulatory proteins (G proteins) transduce a remarkably diverse group of extracellular signals to a relatively limited number of intracellular target enzymes. In the neutrophil, transduction of the signal following fMet-Leu-Phe receptor-ligand interaction is mediated by a pertussis toxin substrate (Gi) that activates inositol-specific phospholipase C. We have utilized a plasma membrane-containing fraction from unstimulated human neutrophils as the target enzyme to explore the role of G proteins in arachidonate and cytosolic cofactor-dependent activation of the NADPH-dependent O-2-generating oxidase. When certain guanine nucleotides or their nonhydrolyzable analogues were present during arachidonate and cytosolic cofactor-dependent activation, they exerted substantial dose-dependent effects. The GTP analogue, GTP gamma S, caused a 2-fold increase in NADPH oxidase activation (half-maximal stimulation, 1.1 microM). Either GDP or its nonhydrolyzable analogue, GDP beta S, inhibited up to 80% of the basal NADPH oxidase activation (Ki GDP = 0.12 mM, GDP beta S = 0.23 mM). GTP caused only slight and variable stimulation, whereas F-, an agent known to promote the active conformation of G proteins, caused a 1.6-fold stimulation of NADPH oxidase activation. NADPH oxidase activation in the cell-free system was absolutely and specifically dependent on Mg2+. Although O2- production in response to fMet-Leu-Phe was inhibited greater than 90% in neutrophils pretreated with pertussis toxin, cytosolic cofactor and target oxidase membranes from neutrophils treated with pertussis toxin showed no change in basal- or GTP gamma S-stimulated NADPH oxidase activation. Cholera toxin treatment of neutrophils also had no effect on the cell-free activation system. Our results suggest a role for a G protein that is distinct from Gs or Gi in the arachidonate and cytosolic cofactor-dependent NADPH oxidase cell-free activation system.
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PMID:Regulation of neutrophil NADPH oxidase activation in a cell-free system by guanine nucleotides and fluoride. Evidence for participation of a pertussis and cholera toxin-insensitive G protein. 302 97

We have studied the interaction of guanine nucleotides with alpha 1-adrenergic receptors of two cloned cell lines, the Madin Darby canine kidney (MDCK-D1) cells and BC3H-1 muscle cells. Although guanylylimidodiphosphate, Gpp(NH)p, had no effect on the affinity or the total number of [3H]prazosin-binding sites in membranes prepared from these cells, the nucleotide decreased the apparent affinity of the agonists (-)-epinephrine and (-)-norepinephrine in competing for [3H]prazosin-binding sites in both cell types. A maximal effect of Gpp(NH)p occurred at 10 microM. Guanine nucleotides were significantly more effective in shifting agonist affinity for the alpha 1 receptor than adenine nucleotides, and Mg2+ was required to observe a maximal effect. Binding of agonist to alpha 1-adrenergic receptors activated phosphatidylinositol (PI) hydrolysis in both cell types but had no effect on membrane adenylate cyclase activity. Incubation of MDCK cells for 19 hr with 100 ng/ml pertussis toxin, which eliminated the ability of pertussis toxin added to membranes to ADP-ribosylate 39-41-KDa substrate(s), failed to alter binding of agonists to alpha 1-adrenergic receptors, the ability of Gpp(NH)p to regulate agonist binding to these receptors, or epinephrine-stimulated PI hydrolysis and prostaglandin E2 production. Incubation of BC3H1 cells with pertussis toxin had no effect on the ability of epinephrine to stimulate PI turnover. These results show that binding of agonists to alpha 1-adrenergic receptors in mammalian kidney and muscle cells is regulated by guanine nucleotides, presumably by interaction with a guanine nucleotide-binding (G) protein. The failure of the G-protein to regulate adenylate cyclase activity and the lack of effect of pertussis toxin to alter receptor-mediated binding or functional activity suggests that a G-protein other than Gs, Gi, or Go interacts with alpha 1-adrenergic receptors in kidney and smooth muscle.
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PMID:Alpha 1-adrenergic receptor-linked guanine nucleotide-binding protein in muscle and kidney epithelial cells. 302 23

Intact neutrophils appear to exhibit interconverting formyl peptide receptor states. The first may be active in transduction and has a dissociation half-time of less than 10 sec. The second appears to be inactive and has a dissociation half-time of approximately 2 min. Neutrophil signals and responses are transient following "pulse" stimulation (when the stimulus is presented and then rapidly removed). The responses decay to baseline following a latency period comparable to the lifetime of the activated receptor. These results are consistent with the notion of transient interconverting receptor states and are discussed in terms of the biochemistry and amplification of the cell activation pathways. We examined the effect of guanine nucleotides on ligand-receptor dynamics at 37 degrees C in neutrophils permeabilized with digitonin, using continuous fluorometric measurements. The permeabilized cells exhibit a single class of slowly-dissociating receptor with a half-time similar to the inactive state. When guanine nucleotide is added, the receptors dissociate with a half-time similar to the first state. The effect of guanine nucleotide is inhibited by Ca++ concentrations above 10 microM. When receptors in permeabilized cells are ADP-ribosylated in the presence of pertussis toxin, the rapidly dissociating state is detected. These results suggest that the dynamics of ligand-receptor interaction under physiological conditions are controlled by a pertussis-toxin-sensitive guanine-nucleotide-binding protein. Guanine nucleotide regulates interconverting states of the formyl peptide receptor and mimics the dynamic states of the receptor observed in the intact cell during stimulation. A model which accounts for these data is described.
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PMID:Ligand-receptor dynamics and signal amplification in the neutrophil. 311 62

Adenosine Ri receptors and inhibitory guanine-nucleotide-regulatory components were solubilized from rat cerebral-cortical membranes with sodium cholate. (-)-N6-Phenylisopropyl[2,8-3H]adenosine [( 3H]PIA) binds with high affinity to the soluble receptors, which retain the pharmacological specificity of adenosine Ri receptors observed in membranes. The binding is regulated by bivalent cations and guanine nucleotides. Bivalent cations increase [3H]PIA binding by increasing both the affinity and the apparent number of receptors. Guanine nucleotides decrease agonist binding by increasing the dissociation of the ligand-receptor complex. Adenosine agonists stabilize the high-affinity form of the soluble receptor. The hydrodynamic properties of the adenosine receptor were determined with cholate extracts of membranes that were treated with [3H]PIA. Sucrose-gradient-centrifugation analysis indicates that the receptor has a sedimentation coefficient of 7.7 S. The receptor is eluted from Sepharose 6B columns with an apparent Stokes radius of 7.2 nm. Labelling of either sucrose-gradient or gel-filtration-column fractions with pertussis toxin and [32P]-NAD+ reveals that both the 41,000- and 39,000-Mr substrates overlap with the receptor activity. These studies suggest that the high-affinity adenosine-receptor-binding activity in the cholate extract represents a stable R1-N complex.
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PMID:Hydrodynamic properties of adenosine Ri receptors solubilized from rat cerebral-cortical membranes. 343 74

Analysis of [3H]quinuclidinyl benzilate/acetylcholine competition curves indicated that the agonist acetylcholine bound with three different affinities to chick heart muscarinic receptors. The estimated KD values for acetylcholine were 2.7, 240, and 4000 nM. Mg2+ increased and guanosine 5'-(beta, gamma-imino)triphosphate (Gpp(NH)p) decreased the proportion of the receptors in the highest affinity state without altering the KD values. Monovalent cations increased the KD values of the three affinity states and obscured the detection of the highest affinity state. The nature of the three affinity states and the sites of action of Mg2+, guanine nucleotides, and monovalent cations were probed with three experimental protocols. Treatments with N-ethylmaleimide or pertussis toxin eliminated both the highest affinity state and the sensitivity to Gpp(NH)p. In contrast, partial effects of Mg2+ were retained after either of these treatments. The effects of monovalent cations on the affinity of the receptor for agonists were unaffected by both treatments. Solubilization of the receptors with digitonin-cholate yielded preparations displaying only the low affinity state for agonist. Agonist binding to the solubilized receptors was insensitive to Mg2+ and guanine nucleotides but retained sensitivity to monovalent cations. The results indicate that chick heart muscarinic receptors can exist in vitro in three agonist affinity states and that the entire population of receptors can be interconverted from one state to another by Mg2+ and guanine nucleotides. Guanine nucleotides presumably act via the inhibitory guanine nucleotide-binding regulatory (Ni) protein, whereas there appear to be at least two distinct sites of action of Mg2+. One site is associated with Ni. Another is distinguishable from Ni but does not appear to be on the receptor itself. The effect of monovalent cations on the interaction of agonists with cardiac muscarinic receptors is qualitatively different and mediated at distinct sites from the effects of Mg2+ and guanine nucleotides.
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PMID:Agonist interactions with cardiac muscarinic receptors. Effects of Mg2+, guanine nucleotides, and monovalent cations. 405 21

Guanine nucleotide regulation of membrane adenylate cyclase activity was uniquely modified after exposure of 3T3 mouse fibroblasts to low concentrations of islet-activating protein (IAP), pertussis toxin. The action of IAP, which occurred after a lag time, was durable and irreversible, and was associated with ADP-ribosylation of a membrane Mr = 41,000 protein. GTP, but not Gpp(NH)p, was more efficient and persistent in activating adenylate cyclase in membranes from IAP-treated cells than membranes from control cells. GTP and Gpp(NH)p caused marked inhibition of adenylate cyclase when the enzyme system was converted to its highly activated state by cholera toxin treatment or fluoride addition, presumably as a result of their interaction with the specific binding protein which is responsible for inhibition of adenylate cyclase. This inhibition was totally abolished by IAP treatment of cells, making it very likely that IAP preferentially modulates GTP inhibitory responses, thereby increasing GTP-dependent activation and negating GTP-mediated inhibition of adenylate cyclase.
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PMID:Guanine nucleotide activation and inhibition of adenylate cyclase as modified by islet-activating protein, pertussis toxin, in mouse 3T3 fibroblasts. 630 74

Chinese hamster ovary (CHO) cells expressing recombinant human m1 (CHO-m1 cells), m2 (CHO-m2 cells), or m3 (CHO-m3 cells) muscarinic receptors were characterised pharmacologically with [3H]N-methylscopolamine. Agonist-stimulated coupling of these receptors with guanine nucleotide-binding proteins (G proteins) was measured by guanine nucleotide- and pertussis toxin-modification of carbachol competition-binding curves, and pertussis toxin-sensitivity of agonist-stimulated [35S]guanosine 5'-O-(3-thiotriphosphate) ([35S]GTP gamma S) binding, in membrane preparations of the CHO cell clones. High affinity agonist binding and agonist-stimulated [35S]GTP gamma S binding was abolished in CHO-m2 cell membranes (expressing 99 +/- 25 fmol of [3H]N-methylscopolamine binding sites/mg protein) after pertussis toxin pretreatment of cells, suggesting that muscarinic m2 receptors expressed in these cell membranes couple predominantly with pertussis toxin-sensitive G proteins. CHO-m1 (713 +/- 102 fmol/mg protein) and CHO-m3 (1212 +/- 279 fmol/mg protein) cell membranes produced smaller elevations in agonist-stimulated [35S]GTP gamma S binding considering the higher receptor levels, compared with CHO-m2 cell membranes. Pertussis toxin pretreatment of these clones also resulted in a significant attenuation of agonist-stimulated [35S]GTP gamma S binding suggesting that, under these experimental conditions, muscarinic m1 and m3 receptors can couple with both pertussis toxin-sensitive and pertussis toxin-insensitive G proteins. Guanine nucleotide-modification of agonist binding in CHO-m1 and CHO-m3 cell membranes was comparatively smaller than in CHO-m2 cell membranes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Coupling of muscarinic m1, m2 and m3 acetylcholine receptors, expressed in Chinese hamster ovary cells, to pertussis toxin-sensitive/insensitive guanine nucleotide-binding proteins. 762 8

Enhanced salt reabsorption by the kidney, which may arise from impaired regulation of proximal tubule Na(+)-K(+)-ATPase activity, has a central role in the pathogenesis of essential hypertension. Guanine nucleotide binding proteins (G proteins) are involved in many regulatory pathways and have been implicated in the regulation of proximal tubule Na(+)-K(+)-adenosinetriphosphatase (ATPase) activity. The present study was designed to evaluate further the regulation of Na(+)-K(+)-ATPase activity by G proteins in proximal tubule suspensions from Wistar-Kyoto rats (WKY) and to determine whether such regulation is abnormal in spontaneously hypertensive rats (SHR). Cholera toxin (CTX) inhibited Na(+)-K(+)-ATPase activity by approximately 40% in WKY but had no effect on Na(+)-K(+)-ATPase activity in SHR. In WKY, pretreatment of tubules with pertussis toxin (PTX), followed by the application of dopamine, inhibited Na(+)-K(+)-ATPase activity significantly, compared with the inhibition produced by dopamine alone. In SHR, dopamine alone did not inhibit Na(+)-K(+)-ATPase activity. However, in the presence of PTX, dopamine inhibited Na(+)-K(+)-ATPase activity significantly. These studies indicate that the renal proximal tubule Na(+)-K(+)-ATPase in WKY is regulated by both a PTX- and CTX-sensitive G protein(s) and that this regulation is abnormal in SHR. Such a defect could cause enhanced sodium reabsorption in SHR and contribute to the pathogenesis of hypertension in this model.
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PMID:Abnormal regulation of renal proximal tubule Na(+)-K(+)-ATPase by G proteins in spontaneously hypertensive rats. 781 Jun 94

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