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)

Human erythroleukaemia (HEL) cells were investigated to characterize their alpha 2-adrenoceptor and imidazoline receptor sites. Membranes from HEL cells bound [3H]2-(2-methoxy-1, 4-benzodioxan-2yl)-2-imidazoline ([3H]RX821002) in a saturable and specific manner with a KD of 0.64 +/- 0.07 nM and a Bmax of 126 +/- 4 fmol/mg protein. [3H]RX821002 was displaced from HEL membranes by adrenergic drugs with the order of potency being yohimbine approximately oxymetazoline >> prazosin = 2-[2-[4-(o-methoxyphenyl)piperazin-1-yl]ethyl]-4,4-dimethyl- 1,3(2H,4H)-isochinolindione HCl (ARC 239), consistent with this site being an alpha 2A-adrenoceptor. HEL membranes also bound [3H]idazoxan in the presence of adrenaline to block alpha 2-adrenoceptors. This binding was saturable and specific with a KD of 3.5 +/- 1.0 nM and a Bmax of 31 +/- 6 fmol/mg protein. Adrenergic drugs from both the phenylethylamine and imidazoline classes increased high-affinity GTPase activity, an index of activation of regulatory heterotrimeric guanine-nucleotide binding proteins (G-proteins), and produced increases in cytosolic free calcium concentration ([Ca2+]i). The effects of these agonists in both systems were abolished by pertussis toxin pretreatment, and oxymetazoline and clonidine were antagonists. The potency of adrenergic drugs to inhibit 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK 14304)-induced increases in [Ca2+]i was yohimbine approximately oxymetazoline >> ARC 239, consistent with the binding data and an action at alpha 2A-adrenoceptors. No evidence was found for a role of imidazoline receptors in stimulating G-proteins or modulating [Ca2+]i. The adrenergic agonist-induced increases in [Ca2+]i were due to both release of Ca2+ from intracellular stores and entry of extracellular Ca2+. Ca2+ entry was blocked by 1-(beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenylethyl)-1H- imidazole hydrochloride (SKF 96365), but not by nitrendipine. Adrenaline also stimulated Mn2+ entry in HEL cells. Taken together, these results suggest that HEL cells have alpha 2A-adrenoceptors that activate non-selective cation channels via pertussis toxin-sensitive G-proteins, i.e. Gi-proteins.
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PMID:Alpha 2A-adrenoceptors mediate activation of non-selective cation channels via Gi-proteins in human erythroleukaemia (HEL) cells. No evidence for a functional role of imidazoline receptors in modulating calcium. 753 Sep 55

A single-step chromatography on Matrex-Gel Blue A has been employed to obtain soluble extracts containing some of the most important antigens of Bordetella pertussis, pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (69-kDa outer membrane protein), fimbriae (FIM2 and FIM3) and adenylate cyclase (AC). Two supernatants, P19 (48.8 mg PT, 6.8 mg FHA, 17.3 mg AC, 13 mg FIM2 and 4.9 mg FIM3 per liter) and P21 (0.1 mg PT, 0.07 mg FHA, 0.46 mg FIM2 and 0.94 mg FIM3 per liter), resulting from bacteria grown in Stainer-Scholte medium, were submitted to chromatography. Fractions with the antigens were obtained after stepwise elution with 60 mM sodium phosphate buffer, pH 6.0; 50 mM Tris-HCl, pH 7.4; 50 mM Tris-HCl, pH 7.4/0.75 M MgCl2; 50 mM Tris-HCl, pH 7.4/4 M MgCl2 and 4 M urea. Preparations from P19 (containing 4.05 micrograms PT, 8.14 micrograms FHA, 6.3 micrograms AC, 3.37 micrograms 69-kDa, 9.54 micrograms FIM2 and 2.23 micrograms FIM3) and from P21 (with 0.175 micrograms PT, 0.28 micrograms FHA, 0.002 micrograms 69-kDa, 0.005 micrograms FIM2 and 0.122 micrograms FIM3) were detoxified with glutaraldehyde and tested as an acellular pertussis vaccine. These products were non-toxic for mice and induced high levels of antibodies against purified pertussis antigens, as judged by ELISA.
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PMID:A Bordetella pertussis acellular vaccine candidate: antigenic characterization and antibody induction. 754 83

Previous studies have shown that fibronectin (Fn) enhances phagocytosis and killing of antibody-coated bacteria by neutrophils and macrophages. In an attempt to understand the mechanism of this enhancement, we have investigated the effects of Fn on phagocytosis-related actin organization as well as respiratory burst activity in neutrophils, monocytes and culture-derived macrophages. Employing an NBD-phallacidin flow cytometric analysis of filamentous actin formation, we found that Fn promotes rapid actin polymerization within 30 seconds in neutrophils, monocytes, and macrophages, but not lymphocytes. Enhancement of actin polymerization by Fn was concentration-dependent and mediated by a pertussis toxin- but not cholera toxin-sensitive G protein. Inhibition of protein kinase C by sphingosine (20 microM), calcium influx by verapamil (0.1 mM), or intracellular calcium mobilization by 8-(N,N-diethyl-amino) octyl-3,4,5-trimethoxybenzoate HCl (TMB-8; 0.1 mM) did not block Fn-enhanced actin polymerization in phagocytes. Incubation of neutrophils and macrophages on microtiter plates precoated with Fn suppressed superoxide (O2-) production induced by IgG- and IgA- opsonized group B streptococci. In contrast, Fn significantly enhanced IgA- and IgG-mediated O2- production by freshly isolated monocytes. These data suggest that Fn enhances phagocytosis, presumably through G protein-coupled cytoskeleton reorganization and augments O2- production by circulating monocytes. In contrast, it appears to suppress O2- production by the active phagocytic cells, neutrophils and macrophages. This may result in enhanced phagocytosis and intracellular killing of microorganisms without damaging interstitial tissues.
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PMID:Effects of fibronectin on actin organization and respiratory burst activity in neutrophils, monocytes, and macrophages. 810 71

The adk gene from the Gram-negative pathogen Bordetella pertussis was cloned by complementing the thermosensitive Escherichia coli adk strain CR341T28. B. pertussis adenylate kinase is a 218-amino-acid protein that has high similarity with adenylate kinase from Escherichia coli and Hemophilus influenzae (57%). A distinct characteristic of enzyme from B. pertussis, not found in other bacterial adenylate kinases, is the presence of a tryptophan residue at position 185. Although distant from the catalytic site, this single tryptophan serves as a convenient probe for monitoring the binding of nucleotide substrates or analogs to the enzyme. Differential scanning calorimetry and equilibrium unfolding experiments in guanidine.HCl indicate similar stabilities for adenylate kinase from B. pertussis and E. coli. An extensive comparison between physico-chemical properties of adenylate kinase from B. pertussis and the enzyme from E. coli showed that the kinetic and structural properties of the two enzymes are very similar. However, infrared spectroscopy has allowed to identify small but significant differences in the secondary structure of the two proteins.
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PMID:Structural and physico-chemical characteristics of Bordetella pertussis adenylate kinase, a tryptophan-containing enzyme. 828 44

The pathogenicity of uveal tissue and melanin has been a controversial subject for a long time. The present new approach has elucidated some of the problems. Melanin granules have been extracted from bovine choroid, iris, hair and skin, and from human, monkey and rabbit choroid. The melanin granules have further been purified by detergent extractions, and are free from pathogenic retinal antigens. Lewis rats immunized with microgram doses bovine choroidal or iris melanin-protein (in Freund's complete adjuvant or Hunter's adjuvant, combined with pertussis toxin) develop severe experimental autoimmune anterior uveitis (EAAU). No retinitis or pinealitis is found. The other melanins are weakly uveitogenic or inactive. The relative pathogenicity of the various melanins seems to be related to tissue and species specificity. The responsible hypothetic pathogenic structure UP-X (uveal pathogen X) is highly stable and resists proteolytic digestion by various enzymes. Its pathogenic activity is destroyed by hot 6 N HCl or longlasting 0.5 N NaOH treatment. In view of its chemical and immunological features it is probably identical to the pathogen PEP-X of bovine retinal pigment epithelial melanin. UP-X-induced EAAU can be transferred by spleen cells, and is suppressed by cyclosporin showing that a T-cell-mediated pathogenic mechanism predominates. It resembles human anterior uveitis by its specific location, its transient nature, and sparing of the retina. In these respects EAAU differs from retinal photoreceptor antigen-induced forms of EAU where retinitis with photoreceptor damage is a main feature. The involvement of melanin in human ocular diseases is discussed.
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PMID:Experimental autoimmune anterior uveitis (EAAU). III. Induction by immunization with purified uveal and skin melanins. 850 May 66

Estrogen, like other steroids, may induce rapid nongenomic cellular effects. We studied the effect on intracellular cAMP of short-term exposure (5 min) of cultured rat pulmonary vascular smooth muscle cells (VSMC) to estradiol 17 beta. At confluence, VSMC were incubated in phosphate buffer saline for 1 hr before exposure to different hormones. The reaction was stopped with 0.1 N HCl and cyclic adenosine monophosphate (cAMP) was measured by radioimmunoassay. The 5-min incubation with estradiol 17 beta (0.3-30 microM) significantly increased basal intracellular cAMP in a concentration-dependent manner. The stimulatory effect of estradiol on cAMP was time-dependent, increasing with prolonged exposure to the hormone, and was not affected by the protein synthesis inhibitor, actinomycin D (5 micrograms/ml), at 5 and 30 min. Comparable concentrations of testosterone or estradiol 17 alpha had no significant effect on cAMP. The estrogen receptor partial agonist, tamoxifen also significantly increased basal cAMP in a concentration-dependent manner, but inhibited the effect of estradiol. Furthermore, forskolin elicited a concentration-dependent increase in cAMP (396.6 +/- 53% at 10 microM concentration), which was significantly potentiated in presence of estradiol. The effect of estradiol is unlikely to be mediated by G-protein activation, because the G protein inhibitor, pertussis toxin (100 ng/ml), did not significantly affect estradiol-induced increase in cAMP. Removal of Ca++ from the incubation medium inhibited the stimulatory effect of estradiol 17 beta suggesting that estradiol may increase pulmonary VSMC cAMP via a Ca(++)-dependent pathway. We suggest that the effect of estradiol 17 beta in these experiments is nongenomic in nature, and is possibly mediated by direct interaction of the hormone with specific membrane binding sites.
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PMID:Estradiol increases cyclic adenosine monophosphate in rat pulmonary vascular smooth muscle cells by a nongenomic mechanism. 863 33

We investigated the effect of dopamine on the vascular Na+-pump activity in isolated rat tail artery sections. Effect of dopamine on vascular tone was also assessed using a perfused tail artery preparation. Dopamine inhibited the Na+-pump activity in isolated rat tail arteries in a dose-dependent manner. Both SKF-38393 HCl, a selective dopamine D1 receptor agonist, and quinpirole HCl, a selective dopamine D2 receptor agonist inhibited the Na+-pump activity. The inhibition of the Na+-pump activity. The inhibition of the Na+-pump by dopamine was accompanied with a transient increase in the vascular tone. SKF-38393, but not quinpirole produced a sustained increase in the vascular tone. Tissues preincubated simultaneously with SCH-23390 HCl, a selective dopamine D1 receptor antagonist, and sulpiride, a selective dopamine D2 receptor antagonist, prevented the dopamine inhibition of the Na+-pump activity. Pertussis toxin blocked the Na+-pump inhibition produced by the dopamine D1 receptor agonist but not by the dopamine D2 agonist. Similarly, the dopamine D1 receptor but not dopamine D2 agonist increased the rate of phosphoinositide hydrolysis in rat tail artery sections. Our results indicate that dopamine inhibition of the Na+-pump is mediated by a pertussis toxin-sensitive mechanism and may be coupled to the activation of the phospholipase C system in rat tail arteries. The modulation of the Na+-pump by dopamine may contribute to the vascular tone.
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PMID:Regulation of Na(+)-pump activity by dopamine in rat tail arteries. 866 11

The coupling of the endogenously expressed alpha2A-adrenoceptors in human erythroleukemia cells (HEL 92.1.7) to Ca2+ mobilization and inhibition of forskolin-stimulated cAMP production was investigated. The two enantiomers of medetomidine [(+/-)-[4-(1-[2, 3-dimethylphenyl]ethyl)-1H-imidazole]HCl] produced opposite responses. Dexmedetomidine behaved as an agonist in both assays (i.e. , it caused Ca2+ mobilization and depressed forskolin-stimulated cAMP production). Levomedetomidine, which is a weak agonist in some test systems, reduced intracellular Ca2+ levels and further increased forskolin-stimulated cAMP production and therefore can be classified as an inverse agonist. A neutral ligand, MPV-2088, antagonized responses to both ligands. Several other, chemically diverse alpha2-adrenergic ligands also were tested. Ligands that could promote increases in Ca2+ levels and inhibition of cAMP production could be classified as full or partial agonists. Their effects could be blocked by the alpha2-adrenoceptor antagonist rauwolscine and by pertussis toxin treatment. Some typical antagonists such as rauwolscine, idazoxan, and atipamezole had inverse agonist activity like levomedetomidine. The results suggest that the alpha2A-adrenoceptors in HEL 92.1.7 cells exist in a precoupled state with pertussis toxin-sensitive G proteins, resulting in a constitutive mobilization of intracellular Ca2+ and inhibition of cAMP production in the absence of agonist. This constitutive activity can be antagonized by inverse agonists such as levomedetomidine and rauwolscine. Levomedetomidine can be termed a "protean agonist" because it is capable of activating uncoupled alpha2-adrenoceptors in other systems and inhibiting the constitutive activity of precoupled alpha2-adrenoceptors in HEL 92.1. 7 cells. With this class of compounds, the inherent receptor "tone" could be adjusted, which should provide a new therapeutic principle in receptor dysfunction.
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PMID:Protean agonism at alpha2A-adrenoceptors. 958 24

An ability of tea catechins known as agents for the disinfection to bacteria and viruses were tested on application for toxoiding biologically active components of Bordetella pertussis. The effects on the activities and antigenicity of filamentous hemagglutinin (FHA) and pertussis toxin (PT) were investigated. The activities of FHA and PT were inactivated by catechins at approximately 10(3) times lower dose (0.2 mM) compared with that of formalin. The activity of inactivated FHA was recovered by dialysis against Tris-HCl buffer, pH 8.0, containing glutathione or Tris-HCl buffer, pH 6.0. But the activity of inactivated PT was not recovered. Antigenicity of catechin-treated antigens were investigated by immunization to mice. The sera from mice immunized by catechin-treated FHA or PT were contained antibody against not only catechin-treated but also non-treated FHA or PT. These results suggest that antigenicity of FHA or PT was not destroyed by the treatment with catechin. We prepared pertussis-component vaccines by treatment of several catechins on the condition that FHA or PT activity was not recovered. Higher efficacy were found on the vaccines made by treatment of epicatechin, epicatechin gallate, or epigallocatechin than those by formalin. The vaccine prepared by using epigallocatechin gallate had significant efficacy as well as that by formalin treated one. From these results, it is suggested that tea leaf catechins were effective agents for toxoiding of vaccine components.
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PMID:[Inactivation and toxoiding of biologically-active components of Bordetella pertussis by tea catechins]. 977 2

The agonist profiles for Ca++ elevations mediated by the human alpha-2 adrenoceptor subtypes alpha-2A, alpha-2B and alpha-2C were compared in the clones of Chinese hamster ovary cells expressing comparable numbers of receptors. No difference was seen between the different clones with respect to the maximum Ca++ mobilizations or the concentrations producing half-maximal stimulation in response to noradrenaline. Ca++ elevations were sensitive to phospholipase C inhibitor U-73122 (1-[6-([17beta]-3-methoxyestra-1,3, 5[10]-trien-17-yl)aminohexyl]-1H-pyrrole-2,5-dione) and pertussis toxin-pretreatment. Although noradrenaline was equally potent and active in all the clones, marked differences in the response to the other agonists were seen. UK14,304 (5-bromo-N-[4, 5-dihydro-1H-imidazol-2-yl]-6-quinoxalinamine) was a full agonist (when compared to noradrenaline) for alpha-2A and alpha-2C, D-medetomidine ([+]-[S]-[4-(1-[2, 3-dimethylphenyl]ethyl)-1H-imidazole]HCl) was a full agonist for alpha-2B and alpha-2C and oxymetazoline (3-[(4, 5-dihydro-1H-imidazol-2-yl-)methyl]-6-[1,1-dimethylethyl]-2, 4-dimethylphenol HCl) was a full agonist only for alpha-2B receptors. Clonidine (2-[2,6-dichloroaniline]-2-imidazoline HCl) was a partial agonist in all the cases; almost no response to this ligand was obtained in the alpha-2B-expressing cells. When the Ca++ responses are compared to the previously published results on cAMP inhibition in Chinese hamster ovary cells, clonidine seems to be significantly less efficacious in elevating Ca++ than in decreasing cAMP.
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PMID:Ligand- and subtype-selective coupling of human alpha-2 adrenoceptors to Ca++ elevation in Chinese hamster ovary cells. 980 94


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