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)

1. Intracellular recordings were obtained from submucous plexus neurones of the guinea-pig caecum. 2. The resting membrane conductance displayed two types of inward rectification: one which developed at potentials more negative than -70 mV, and another that occurred at potentials more negative than the potassium equilibrium potential. The former inward rectification was blocked by extracellular caesium (Cs+; 1-2 mM) and the latter was blocked by Cs+ (1-2 mM) or barium (Ba2+; 30-100 microM). 3. The noradrenaline-induced current measured by subtraction of the current-voltage (I-V) relation before and after adding the agonist also showed an inward rectification around the resting potential. Ba2+ (30-100 microM) blocked both the outward and inward current induced by noradrenaline. The noradrenaline current was not affected by Cs+ (1-2 mM). Both the slow IPSP and the slow IPSC (inhibitory postsynaptic current) were reduced by Ba2+, but not by Cs+. 4. During the intracellular injection of guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S), multiple repetitive stimulation or repeated applications of noradrenaline produced irreversible membrane hyperpolarizations with a decreased membrane input resistance, until the membrane had approached the potassium equilibrium potential. 5. Pertussis toxin (1-40 micrograms/ml) abolished both the slow IPSP and the noradrenaline hyperpolarization without affecting the nicotinic fast EPSP or the slow EPSP. 6. Superfusion with a Ca(2+)-free, high-Mg2+ (12 mM) solution caused a membrane depolarization associated with an increased input resistance. It eliminated the Ca2+ spikes, the slow after-hyperpolarizations following the spikes, and the synaptic potentials within 3 min. Prolonged exposure (longer than 20 min) to this solution resulted in a progressive decline of the noradrenaline hyperpolarization. 7. Intracellular injection of ethylene glycol-bis(beta-aminoethylether)N,N,N',N'-tetraacetic acid (EGTA) reduced the slow IPSP and the noradrenaline hyperpolarization. Superfusion with a membrane-permeable Ca2+ chelator, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, tetraacetoxymethyl ester (BAPTA/AM; 10-200 microM) reduced the noradrenaline hyperpolarization. 8. Procaine reversibly reduced the slow IPSP and noradrenaline hyperpolarization without affecting the fast EPSP or slow EPSP at concentrations up to 300 microM.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Mechanisms underlying intracellular signal transduction of the slow IPSP in submucous neurones of the guinea-pig caecum. 206 48

Cloning of a complementary DNA (cDNA) for Gz alpha, a newly appreciated member of the family of guanine nucleotide-binding regulatory proteins (G proteins), has allowed preparation of specific antisera to identify the protein in tissues and to assay it during purification from bovine brain. Additionally, expression of the cDNA in Escherichia coli has resulted in the production and purification of the recombinant protein. Purification of Gz from bovine brain is tedious, and only small quantities of protein have been obtained. The protein copurifies with the beta gamma subunit complex common to other G proteins; another 26-kDa GTP-binding protein is also present in these preparations. The purified protein could not serve as a substrate for NAD-dependent ADP-ribosylation catalyzed by either pertussis toxin or cholera toxin. Purification of recombinant Gz alpha (rGz alpha) from E. coli is simple, and quantities of homogeneous protein sufficient for biochemical analysis are obtained. Purified rGz alpha has several properties that distinguish it from other G protein alpha subunit polypeptides. These include a very slow rate of guanine nucleotide exchange (k = 0.02 min-1), which is reduced greater than 20-fold in the presence of mM concentrations of Mg2+. In addition, the rate of the intrinsic GTPase activity of Gz alpha is extremely slow. The hydrolysis rate (kcat) for rGz alpha at 30 degrees C is 0.05 min-1, or 200-fold slower than that determined for other G protein alpha subunits. rGz alpha can interact with bovine brain beta gamma but does not serve as a substrate for ADP-ribosylation catalyzed by either pertussis toxin or cholera toxin. These studies suggest that Gz may play a role in signal transduction pathways that are mechanistically distinct from those controlled by the other members of the G protein family.
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PMID:Gz, a guanine nucleotide-binding protein with unique biochemical properties. 210 21

The native pertussis toxin sensitive GTP-binding proteins (Gi proteins) were individually resolved, and their guanine nucleotide binding and release properties were studied. Gi2 and Gi3, the two major GTP-binding proteins of human erythrocytes, were purified to apparent homogeneity by fast protein liquid chromatography. Gi1 was purified from bovine brain. The three proteins bound 0.6-0.85 mol of guanosine 5'-O-(thio-triphosphate (GTP gamma S)/mol of protein with similar affinities (KD(app) = 50-100 nM). The rate of [35S]GTP gamma S binding to Gi2 was 5-8-fold faster than to Gi1 or Gi3 at 2 mm Mg2+. There were no observable differences in the binding characteristics between bovine brain Gi1 and human erythrocyte Gi3. At 50 mM Mg2+, all three Gi proteins exhibited fast binding, although Gi1 and Gi3 were marginally slower than Gi2. All three Gi proteins exhibited different rates of [32P]GDP release at 2 mM Mg2+. GDP release from Gi2 was severalfold faster than that from Gi1 or Gi3. GDP release rates from Gi1 and Gi3 were similar, although Gi3 was somewhat (60-80%) faster than Gi1. These data indicate that rates of GDP release and GTP binding may be independently regulated for these three proteins and that the relative proportions of Gi2/Gi1 or Gi2/Gi3 will be a crucial factor in determining the kinetics of signal transduction through Gi-coupled effectors.
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PMID:Distinct guanine nucleotide binding and release properties of the three Gi proteins. 210 58

Electropermeabilization creates small pores in the plasma membrane allowing the introduction of low-molecular-weight modulatory components, such as ions and nucleotides, into the cytosol. The present study investigates fluoride-mediated stimulation of the signal transduction pathway that activates the respiratory burst in electropermeabilized neutrophils. In marked contrast to intact (i.e., non-electropermeabilized) neutrophils, cells permeabilized by this technique demonstrated an immediate and potent stimulation of the superoxide (O2-)-generating NADPH oxidase in response to the addition of fluoride. Furthermore, permeabilization of neutrophils in the presence of exogenously added ATP enhanced the rate of F(-)-mediated O2- production. Fluoride-stimulated O2- production in electropermeabilized neutrophils was antagonized by GDP beta S and dependent upon the presence of Mg2+ in the medium, but was insensitive to pertussis toxin treatment, consistent with the hypothesis that fluoride activates a G protein, probably Gp, by interacting with the nucleotide-binding site on the G alpha subunit. In addition, electropermeabilized neutrophil O2- release triggered by F- was blocked by staurosporine and H-7, indicating that this pathway proceeds largely through protein kinase C activation. However, nucleotide-enhanced O2- production was only partially blocked by these inhibitors, suggesting that under such conditions ATP either competes with the inhibitor-protein kinase interaction or affects the signaling pathway(s) in such a way that protein kinase C may no longer be necessary for the activation of NADPH oxidase.
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PMID:Fluoride-mediated activation of the respiratory burst in electropermeabilized neutrophils. 211 32

Inhibition of adenylyl cyclases from Bacillus anthrasis and Bordetella pertussis by polyadenylate and by the most potent "P"-site agonists was investigated. These bacterial adenylyl cyclases differed in their sensitivity to inhibition by nominal "P"-site agents and in the effect of divalent cations on this inhibition. The enzyme from Bordetella pertussis was relatively insensitive to inhibition by "P"-site agonists, exhibiting a rank order of potency of 2'd3'AMP greater than 3'-AMP greater than 2',5'-ddAdo approximately Ado approximately 2'-dAdo, with IC50 values for 2'd3'AMP and 3'-AMP of 1-3 mM. Inhibition by 2'd3'AMP, however, was not affected by divalent cation, making it distinct from "P"-site-mediated inhibition of most mammalian adenylyl cyclases. The sensitivity to these nucleosides was comparable with potency for inhibition of bovine sperm adenylyl cyclase but was 3 orders of magnitude less potent than for activated enzyme from bovine or rat brain. The Bordetella pertussis enzyme was similarly insensitive to inhibition by polyadenylate, with 16 microM inhibiting less than 20%. By comparison, Bacillus anthrasis adenylyl cyclase was more potently inhibited by 2'd3'AMP (IC50 approximately 85 microM) but not by the other nucleosides (less than 15% inhibition at 1 mM), and inhibition by 2'd3'AMP was optimally enhanced by 5-10 mM Mg2+ or Mn2+, as is typical for inhibition by "P"-site agonists. The Bacillus anthrasis enzyme was potently inhibited by polyadenylate (IC50 approximately 0.3 microM), comparable to inhibition of brain adenylyl cyclases. Sensitivity of Bacillus anthrasis adenylyl cyclase to poly(A) was diminished somewhat by Ca2+/calmodulin (to IC50 approximately 1 microM) although Ca2+/calmodulin was without effect on inhibition by 2'd3'AMP. In contrast to inhibition of mammalian adenylyl cyclases via the "P"-site, inhibition of both bacterial adenylyl cyclases by 2'd3'AMP was competitive with respect to substrate MgATP. The data indicate basic differences in susceptibilities of these bacterial adenylyl cyclases to inhibition by poly(A), by adenosine analogs, and the effects of divalent cations. Although the potency of 2'd3'AMP and the metal-dependent nature of inhibition of Bacillus anthrasis adenylyl cyclase shared characteristics of "P"-site-mediated inhibition, the fact that inhibition of both bacterial adenylyl cyclases was competitive with respect to substrate strongly suggests that this inhibition was at the catalytic site and that these bacterial enzymes do not contain a distinct "P"-site.
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PMID:Inhibition of Bordetella pertussis and Bacillus anthracis adenylyl cyclases by polyadenylate and "P"-site agonists. 212 33

In primary cultures of sheep pituitary cells extracellular nucleotides stimulated rapid increases in inositol tris- and bisphosphate, accompanied by intracellular Ca2+ mobilization. A similar stimulation of inositol phosphate production by extracellular nucleotides was observed in rat and baboon pituitary cells. The inositol phosphate response to nucleotides was greater than that elicited by any of the known hypothalamic releasing peptides. UTP, ATP, and ATP gamma S were the most potent agonists, with EC50 values for inositol phosphate production of 1.2, 2.6, and 2.7 microM. The relative potencies of a range of nucleotides indicates that the pharmacological specificity of the pituitary nucleotide receptor is different from that of the previously characterized P2X and P2Y purinoceptors present in other tissues. Increasing extracellular Mg2+ concentrations caused a shift to the right of the ATP dose-response curves, indicating that the predominantly active agonist species is not MgATP and may be ATP4-. In the absence of both Ca2+ and Mg2+ (1 mM EDTA) ATP stimulated inositol phosphate production with high potency (EC50 = 200 nM), indicating that an ectokinase or ecto-ATPase reaction is not involved in its mode of action. Phosphoinositidase-C activation by ATP was insensitive to pertussis toxin. The magnitude of the inositol phosphate and 45Ca2+ responses to extracellular nucleotides indicates that a substantial fraction of the cells in primary pituitary cultures bears nucleotide receptors. None of the major pituitary hormones appear to be released by extracellular nucleotides. The cell types in the pituitary that bear these nucleotide receptors are at present unidentified.
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PMID:A novel extracellular nucleotide receptor coupled to phosphoinositidase-C in pituitary cells. 215 80

Myeloid-differentiated HL-60 cells were used to study the activation of G-proteins by receptor agonists. Following incubation of membranes with the photoreactive GTP analog. [alpha-32P]GTP azidoanilide, and subsequent exposure to ultraviolet light (254 nm), photolabeling of 40 kDa proteins comigrating with the Gi2 alpha-subunit was observed. Photolabeling in the absence or presence of the chemoattractant, N-formyl-methionyl-leucyl-phenylalanine (FMLP), absolutely required Mg2+; FMLP stimulated photolabeling at all Mg2+ concentrations employed (up to 30 mM). Addition of GDP (3-50 microM) reduced basal photolabeling to a greater extent than photolabeling stimulated by FMLP. FMLP did not stimulate photolabeling of proteins modified by pertussis toxin. Leukotriene B4 and C5a also stimulated photolabeling of 40 kDa proteins. The results indicate that (i) the major G-protein in HL-60 cells, Gi2, requires Mg2+ for basal and receptor-stimulated activity, (ii) effective receptor-mediated activation of G-proteins is observed at mM concentrations of Mg2+, and (iii) receptor agonists apparently reduce the affinity of G-proteins for GDP.
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PMID:Agonist-sensitive binding of a photoreactive GTP analog to a G-protein alpha-subunit in membranes of HL-60 cells. 215 75

The putative regulatory effect of opioids on adenylate cyclase was investigated in two different preparations containing, respectively, two different populations of opioid receptors: the rabbit cerebellum (greater than 75% mu-opioid receptors) and the guinea pig cerebellum (greater than 80% kappa-opioid receptors). In the mu-preparation, but not in the kappa-preparation, opioids inhibited the basal and the forskolin-stimulated adenylate cyclase activity in a dose-dependent manner and stereospecifically. The inhibition was in the 20-30% range, required the presence in the assay medium of Mg2+ and of GTP, but was independent of the presence of Na+. Pharmacological characterization of the inhibitory response in the rabbit cerebellum clearly showed that it was under the control of a mu-opioid binding site, with the effect being elicited by non-selective (etorphine and morphine) and mu-selective (Tyr-D-Ala-Gly-Me-Phe-Gly-ol) agonists, whereas delta- and kappa-selective agonists were almost totally ineffective. ADP ribosylation of inhibitory GTP-binding protein by pertussis toxin failed to block the inhibitory effect of opioids, and data presented suggest that this failure is likely to be the consequence of a limited access of the toxin to its substrate in rabbit cerebellum membranes.
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PMID:mu-Opioid receptors and not kappa-opioid receptors are coupled to the adenylate cyclase in the cerebellum. 215 54

High affinity GTPase in membranes from NG108-15 cells was differentially affected by opioid competitive antagonists; one type of antagonist [( N,N'-diallyl-Tyr1-Aib2,3]Leu-enkephalin) reduced the basal rate of GTP hydrolysis, whereas a second type (MR 2266) produced no changes. The inhibitory effect of the "active" antagonist was stereospecifically reversed by the "inactive" antagonist, indicating that it was receptor mediated. This suggests that part of basal GTPase activity in this system results from a spontaneous interaction between opioid receptors and GTP-binding proteins (G proteins) and that some antagonists exhibit negative intrinsic activity by hindering such an interaction. The inhibitory effect of the antagonist was minimal in the presence of Na+ and maximal when Na+ was replaced by K+ in the reaction. When the ratio [Na+]/[K+] was progressively increased at constant [Cl-], total GTPase activity (i.e., net difference between activity stimulated by agonist and that inhibited by antagonist) did not change, but the activity measured in the absence of ligand was selectively decreased. Thus, Na+ does not alter the total proportion of G proteins that can be activated by ligand-occupied receptors and instead regulates the interaction between receptor and G protein in the absence of ligand. Upon examination of several opioid agonist and antagonists, we found an inverse relation between the intrinsic activity (either negative or positive) of each ligand and the sensitivity to Na+ of the GTPase elicited upon occupation of the receptor by that ligand. Sodium-mediated and ligand-mediated regulations of GTPase had identical requirements for Mg2+ [( Mg2+]free greater than 10 microM), and were both abolished with a similar potency by pertussis toxin. There was no effect of Na+ on the basal rate of GTP hydrolysis of Gi/Go purified from bovine brain. However, addition of these proteins to membranes prepared from cells that had been previously exposed to pertussis toxin partially restored both receptor- and sodium-mediated regulations of GTPase in parallel and in a concentration-dependent fashion. We conclude that sodium ions play a key role in the mechanism underlying the spontaneous interaction between "empty" receptors and G proteins in intact membranes.
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PMID:Spontaneous association between opioid receptors and GTP-binding regulatory proteins in native membranes: specific regulation by antagonists and sodium ions. 215 52

Preparations of rod outer segments from cattle retinas contained soluble and particulate phospholipase C activities which hydrolyzed phosphatidylinositol 4,5-bisphosphate (PIP2) and the other phosphoinositides. Ca2+ was required for PIP2 hydrolysis, but high (greater than 300 microM) concentrations were inhibitory. Mg2+ and spermine at low concentrations stimulated the particulate activity but inhibited the soluble. Mn2+ inhibited both. High (greater than 100 microM) concentrations of the nonhydrolyzable GTP analogue guanylyl beta,gamma-methylenediphosphonate inhibited PIP2 hydrolysis by both the soluble and particulate activities, but guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S), fluoride, and cholera and pertussis toxins were without effect. Overall phospholipase C activity in ROS was unaffected by light. Evidence was found for multiple forms of the enzyme, requiring isolation and separate characterization before ruling out regulation by light or G-protein.
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PMID:Phosphatidylinositol-4,5-bisphosphate phospholipase C in bovine rod outer segments. 216 27

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