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)

Two structurally and immunologically different components of Bordetella pertussis endotoxin can be visualized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and silver staining: a major A band and a faster-migrating minor B band. Certain mutant strains of B. pertussis express only the B band, while the wild-type strains produce both lipooligosaccharides (LOS). Two monoclonal antibodies (MAbs) directed against the minor LOS B band were generated, allowing the study of this surface molecule on different strains of Bordetella. These two MAbs, designated BL-8 and BL-9, reacted strongly with phenol-water-purified LOS obtained from a B. pertussis LOS B mutant strain. Sodium periodate treatment of the purified LOS prevented binding of the MAbs, indicating the carbohydrate nature of the epitope(s). Western immunoblotting experiments revealed that the epitope(s) recognized by these MAbs is conserved on all B. pertussis and Bordetella bronchiseptica Vir- (avirulent) variant strains tested but is not present on Bordetella parapertussis and B. bronchiseptica Vir+ (virulent) wild-type strains. Further studies showed that although present in the lipopolysaccharide B band expressed by Vir- strains, the epitope(s) recognized by the MAbs is not accessible on the surface of intact B. bronchiseptica cells. For B. pertussis, the density and accessibility of this epitope(s) are dependent on the virulence-associated or LOS phenotype expressed by the strain. Our data demonstrate that the expression and accessibility of the epitope(s) are significantly greater on the LOS B variant strains and LOS AB Vir- strains compared with fresh B. pertussis clinical isolates. For these latter strains, which are Vir+, this epitope(s) was barely detectable on the surface of intact bacteria, despite Western blot analyses that revealed specific reactions between the MAbs and the LOS B band. The two LOS B-specific MAbs had no bacteriolytic activity against a LOS AB wild-type strain, while the control MAb BL-2, which is specific for the B. pertussis LOS A band, significantly reduced the number of living bacteria in the same assay. Moderate lytic activity against a mutant strain expressing only the LOS B band was observed for MAb BL-8 but not for MAb BL-9 or BL-2. These data demonstrate that the type, amount, and surface exposure of the LOS are related to the phenotype expressed by a specific B. pertussis strain. In addition, the LOS B MAbs also reveal the antigenic conservation of carbohydrate epitopes among B. pertussis and B. bronchiseptica strains.
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PMID:Immunological characterization of the lipooligosaccharide B band of Bordetella pertussis. 137 81

We sought to assess the effect of an increase in cAMP on sodium channels on adult rat cardiac ventricular myocytes. Sodium channels were studied with the use of the radiolabeled sodium channel-specific toxin [3H] batrachotoxinin benzoate ([3H]BTXB). Forskolin, isoproterenol, prostaglandin E1, cholera toxin, and pertussis toxin each increased cAMP levels and decreased the number of [3H]BTXB binding sites without changing the affinity of [3H]BTXB for the sodium channel. The cAMP analog 8-bromo-cyclic AMP (8-Br-cAMP) reduced the number of [3H]BTXB binding sites from 19 fmol/10(5) cells to 11 fmol/10(5) cells. [3H]BTXB binding site down-regulation was reversible, cAMP dose-dependent, and time-dependent. To test the hypothesis that the cAMP effect was mediated by cAMP-dependent phosphorylation, we determined the effect of 8-Br-cAMP on [3H]BTXB binding after preincubation of myocytes with N-(2-(methylamino)ethyl)-5-isoquinolinesulfonamide dihydrochloride (H8), a protein kinase A inhibitor. H8 inhibited 70% of the decrease in the number of [3H]BTXB binding sites induced by 8-Br-cAMP. Thus increases in intracellular cAMP in cardiac myocytes reversibly induced a decrease in the number of [3H]BTXB binding sites via cAMP-dependent protein phosphorylation, possibly of the sodium channel.
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PMID:Cyclic AMP-dependent regulation of the number of [3H]batrachotoxinin benzoate binding sites on rat cardiac myocytes. 164 46

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

The present study examines the influence of potassium and sodium ions on guanine nucleotide regulation of adenylate cyclase in various brain regions, including the locus coeruleus (LC), dorsal raphe (DR), ventral tegmentum (VT), hippocampus (HP), frontal cortex (FC), substantia nigra (SN), neostriatum (NS) and cerebellum (CB). Guanine nucleotide regulation of adenylate cyclase was highest in the LC, DR and VT and lowest in NS and CB. Sodium and potassium ions were found to stimulate basal or GTP-activated adenylate cyclase in NS and SN, whereas the cations were found to specifically inhibit guanine nucleotide-stimulated enzyme activity in all other brain regions with the exception of CB, where there was no effect. With regard to stimulation of adenylate cyclase, lithium was more potent than sodium which was more potent than potassium in SN and NS. With regard to inhibition of the enzyme, potassium was equipotent to lithium which was greater than sodium in the other brain regions examined. Both stimulatory and inhibitory effects of cations in the different regions were significant (P less than 0.05) at 30 mM and were maximal at 90-120 mM. Sodium ion inhibition of GTP-stimulated adenylate cyclase in LC and DR was partially blocked by pertussis toxin treatment, whereas cation stimulation in NS was not affected by the toxin. The results demonstrate marked region-specific effects of sodium and potassium on adenylate cyclase, which could occur at either G-proteins or the catalytic unit of the enzyme. The possibility that ion fluxes alter G-protein function is discussed.
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PMID:Sodium and potassium regulation of guanine nucleotide-stimulated adenylate cyclase in brain. 254 4

It has previously been shown that neurotensin binds to high-affinity receptors in the adenocarcinoma HT29 cell line, and that receptor occupancy leads to inositol phosphate formation. The present study was designed to investigate further the effects of neurotensin on calcium mobilization and protein kinase C (PKC) activation in HT29 cells, and to assess the role of GTP-binding proteins (G-proteins) in the neurotensin response. Direct measurements of cytosolic Ca2+ variations using the fluorescent indicator quin 2 showed that neurotensin (0.1-1 microM) elicited Ca2+ transients in HT29 cells. These transients occurred after the neurotensin-stimulated formation of Ins(1,4,5)P3, as measured by means of a specific radioreceptor assay. In addition, the peptide induced a decrease in the 45Ca2+ content of cells previously equilibrated with this isotope. The peptide effect was rapid, long-lasting and concentration-dependent, with an EC50 of 2 nM. Phorbol 12-myristate 13-acetate (PMA) inhibited by 50% the neurotensin effects on both intracellular Ca2+ and inositol phosphate levels. The inhibition by PMA was abolished in PKC-depleted cells. Pertussis toxin had no effect on either the Ca2+ or inositol phosphate responses to neurotensin. Epidermal growth factor (EGF) receptors which are present in HT29 cells have been shown to be down-regulated through phosphorylation by PKC in a variety of systems. Here, PMA markedly (70-80%) inhibited EGF binding to HT29 cells. Scatchard analysis revealed that PMA abolished the high-affinity component of EGF binding, an effect that was totally reversed in PKC-depleted cells. In contrast, neurotensin slightly (10-20%) inhibited EGF binding to HT29 cells, and its effect was only partly reversed by PKC depletion. Neurotensin had no detectable effect on sn-1,2-diacylglycerol levels in HT29 cells, as measured by a specific and sensitive enzymic assay. In membranes prepared from HT29 cells, monoiodo[125I-Tyr3]neurotensin bound to a single population of receptors with a dissociation constant of 0.27 nM. Sodium and GTP inhibited neurotensin binding in a concentration-dependent manner. Maximal inhibition reached 80% with Na+ and 35% with GTP.IC50 values were 20 mM and 0.2 microM for Na+ and GTP respectively. Li+ and K+ were less effective than Na+ and the effects of GTP were shared by GDP and guanosine-5'-[beta gamma- imido]triphosphate but not by ATP. Scatchard analysis of binding data indicated that Na+ and GTP converted the high-affinity neurotensin-binding sites into lower affinity binding sites. The properties of the effects of Na+ and GTP on neurotensin-receptor interactions are characteristic of those receptors which interact with G-proteins.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neurotensin stimulates inositol trisphosphate-mediated calcium mobilization but not protein kinase C activation in HT29 cells. Involvement of a G-protein. 255 20

A basophilic leukemic cell line from rat (RBL-1) was used to characterize leukotriene D4 (LTD4) receptor-mediated biochemical and pharmacological effects. [3H]LTD4 binding to the plasma membrane enriched preparation was stereo-selective, specific and saturable. Sodium ions and guanine nucleotides specifically regulated [3H]LTD4 binding to the membrane receptors. Leukotriene E4 (LTE4) and high affinity specific antagonists bound to the receptor with a rank-order potency equivalent to that for the LTD4 receptors in guinea pig lung. In the [3]myoinositol labeled RBL-1 cells, LTD4 and LTE4 induced a rapid hydrolysis of [3H]phosphoinositides. The biosynthesis of the [3H]inositol-trisphosphate was rapid and was detectable at 15-sec poststimulation. The biosynthesis of [3H]inositol-monophosphate was stereo-selective and specific and was inhibited specifically by receptor antagonists. In fura-2 loaded RBL-1 cells, LTD4 and LTE4 induced a transient intracellular Ca++ mobilization. Agonist-induced Ca++ mobilization was specific and stereo-selective and was inhibited by specific receptor antagonists. The most (greater than 85%) LTD4-induced immediate response of Ca++ mobilization was from intracellular sources, whereas a small amount (less than 15%) was derived from the extracellular milieu. Both components were stimulated by receptor agonists and inhibited by the receptor antagonists, suggesting that they were regulated by the LTD4 membrane receptors. In addition, the results also suggested that a guanine nucleotide binding protein, insensitive to islet activating protein from Bordetella pertussis (not Gi or Go), was involved in the signal transduction mechanisms for LTD4 receptors in RBL-1 cells. These results suggested that the plasma membrane enriched LTD4 receptor was coupled via an islet activating protein insensitive G protein to a phosphoinositide specific phospholipase C. Agonist binding to the receptor could activate phospholipase C and resulted in phosphoinositide hydrolysis. Diacylglycerol and inositol trisphosphate could function as intracellular messengers that trigger or contribute to calcium mobilization in RBL-1 cells.
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PMID:Leukotriene D4 receptor-mediated phosphoinositol hydrolysis and calcium mobilization in rat basophilic leukemic cells. 284 29

Sodium and other monovalent cations (added as chloride salts) inhibited adenylate cyclase of luteinized rat ovary. Sodium chloride (150 mM) inhibited basal enzyme activity by 20%. Sodium chloride inhibition was enhanced to 34-54% under conditions of enzyme stimulation by guanine nucleotides (GTP and its nonhydrolyzable analog 5'-guanylyl imidodiphosphate), fluoride anion, and agonists (ovine luteinizing hormone (oLH) and the beta-adrenergic catecholamine isoproterenol) acting at stimulatory receptors linked to adenylate cyclase. Sodium chloride inhibition was dependent on salt concentration over a wide range (25-800 mM) as well as the concentrations of GTP and oLH. Inhibition by NaCl was of rapid onset and appeared to be reversible. The order of inhibitory potency of monovalent cations was Li+ greater than Na+ greater than K+. The role of individual components of adenylate cyclase in the inhibitory action of monovalent cations was examined. Exotoxins of Vibrio cholerae and Bordetella pertussis were used to determine respectively the involvement of the stimulatory and inhibitory guanine nucleotide-binding regulatory components (Ns and Ni) in NaCl inhibition. Sodium chloride inhibited cholera toxin-activated adenylate cyclase activity by 29%. Ni did not appear to mediate cation inhibition of adenylate cyclase because pertussis toxin did not attenuate inhibition by NaCl. Enzyme stimulation by agents (forskolin and Mn2+) thought to activate the catalytic component directly was not inhibited by NaCl but was instead significantly enhanced. Sodium chloride (150 mM) increased both the Kd for high-affinity binding of oLH to 125I-human chorionic gonadotropin binding sites and the Kact for oLH stimulation of adenylate cyclase by sevenfold. In contrast, NaCl had no appreciable effect on either isoproterenol binding to (-)-[125I]iodopindolol binding sites or the Kact for isoproterenol stimulation of adenylate cyclase. The results suggest that in luteinized rat ovary monovalent cations uncouple, or dissociate, Ns from the catalytic component and, in a distinct action, reduce gonadotropin receptor affinity for hormone. Dissociation of the inhibitory influence of Ni from direct catalytic activation could account for NaCl enhancement of forskolin- and Mn2+-associated activities. On the basis of these results, the spectrum of divergent stimulatory and inhibitory effects of monovalent cations on adenylate cyclase activities in a variety of tissues may be interpreted in terms of differential enzyme susceptibilities to cation-induced uncoupling of N and catalytic component functions.
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PMID:Inhibition of adenylate cyclase from luteinized rat ovary by monovalent cations: roles of the stimulatory guanine nucleotide-binding regulatory component and stimulatory hormone receptor. 312 64

We have examined the effects of sodium (Na+) salts on rat liver adenylate cyclase. Increasing concentrations of Na+ salts produced biphasic stimulation and inhibition of adenylate cyclase and potentiated enzyme activation by GTP and its hydrolysis resistant analog 5'-guanylyl imidodiphosphate. Salt effects were temperature dependent, of rapid onset, and specific for the Na+ cation though also partly dependent on the accompanying anion. Sodium salt stimulation of adenylate cyclase and enhancement of GTP activation were attenuated by agents (pertussis toxin and N-ethylmaleimide) which inactivate the inhibitory guanine nucleotide-binding regulatory component (Gi) of adenylate cyclase. Cholera toxin, which activates the stimulatory guanine nucleotide-binding regulatory component (Gs) of adenylate cyclase and thereby increases enzyme activity, augmented the inhibitory phase of Na+ salt action. These results suggest that the stimulatory and inhibitory effects of Na+ salts may be due, respectively, to inhibition of Gi and Gs modulation of adenylate cyclase.
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PMID:Stimulatory and inhibitory effects of sodium salts on adenylate cyclase of rat liver. Implications for salt modulation of guanine nucleotide-binding regulatory component function. 314 74

The sympathetic renal nerves are of central importance for the regulation of sodium balance. Sodium excretion decreases following renal nerve activation and increases following denervation. These effects have been attributed to norepinephrine (NE) acting on alpha-adrenergic receptors. In the present study, using isolated permeabilized rat renal proximal convoluted tubule (PCT) cells, neuropeptide Y (NPY) was shown to stimulate Na+, K(+)-ATPase activity. This 36-amino acid peptide is a messenger molecule in the sympathetic nervous system which is co-stored with NE and dopamine-beta-hydroxylase (DBH), the NE synthesizing enzyme in the renal nerves. The effect is likely to be mediated via the NPY Y2 receptor, a pertussis toxin (PTX)-sensitive G-protein, and calcium. It is partially antagonized by alpha-adrenergic antagonists, and enhanced by the subthreshold doses of alpha-adrenergic agonists. Our results suggest an important role for this peptide in the regulation of the sodium balance in the kidney.
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PMID:Coexisting NPY and NE synergistically regulate renal tubular Na+, K(+)-ATPase activity. 752 51

Studies were performed to determine the primary signal transduction mechanism that mediates adenosine stimulation of electrogenic sodium transport in renal epithelial cells. Experiments were performed on cultured amphibian A6 cells with an adenosine analogue that preferentially binds to the A1 receptor, cyclohexyladenosine (CHA). Sodium transport was assessed by the equivalent short circuit current (Ieq). CHA was found to stimulate Ieq via activation of an A1 receptor because (1) the threshold concentration was 1 nM compared to that of 10 microM for the specific A2 agonist CGS21680, (2) CHA inhibited vasopressin (AVP)-stimulated cAMP production by a pertussis toxin-sensitive mechanism, and (3) the action of CHA was inhibited by the A1 antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX). CHA increased intracellular Ca2+ ([Ca2+]i) and stimulated phosphoinositide turnover at concentrations that increased Ieq and in a time course that paralleled the increase in Ieq. Ion transport was stimulated by a Ca(2+)-dependent mechanism because the CHA induced increase in Ieq was inhibited by chelating [Ca2+]i with 5,5'dimethyl BAPTA in a dose-dependent manner, with a Ki of approximately 10 microM. The increase in Ieq was also dose-dependently inhibited by the specific PKC inhibitors dihydroxychlorpromazine and chelerythrine, and by trifluoperazine which inhibits PKC and calmodulin. Further studies indicated that CHA-stimulated Ieq was independent of cAMP generation because CHA did not induce an increase in cAMP accumulation parallel to the increase in Ieq in a dose-response analysis, and the adenylate cyclase inhibitor 2',5' dideoxy-adenosine (DDA) did not affect the CHA-induced increase in Ieq.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adenosine stimulation of Na+ transport is mediated by an A1 receptor and a [Ca2+]i-dependent mechanism. 764 26

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