Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

It is envisaged that circulating IgA complexes play a primary role in the glomerular injury of IgA nephropathy, the most common glomerulonephritis worldwide. In this study, we examined the pathophysiological effects of IgA and IgG isolated from IgA-nephritic patients on the signal transduction of human neutrophils. Heat-aggregated forms and monomers of IgA and IgG were prepared from sera of 11 IgA-nephritic patients and 11 healthy controls. Signal transduction was studied by measuring the inositol triphosphate (IP3) production in neutrophils incubated with the immunoglobulin preparations. Different forms of IgA or IgG from IgA-nephritic patients failed to induce a significant increase in IP3 production directly as compared with control IgA or IgG. However, neutrophils preincubated with heat-aggregated IgA (HAA) from IgA-nephritic patients demonstrated a significant rise in IP3 production upon subsequent stimulation by a chemotactic peptide, FMet-Leu-Phe (FMLP); a similar finding was not observed with heat-aggregated IgG. HAA pretreatment of neutrophils increased FMLP-induced IP3 production in a dose-dependent manner. The raised IP3 production was not due to increased FMLP receptors, as HAA preincubation of neutrophils did not increase the binding of tritiated FMLP. The increased IP3 production upon FMLP stimulation in HAA-primed neutrophils was completely abolished by pertussis toxin in a dose-dependent manner. These findings tend to refute a direct stimulatory effect of HAA on phospholipase C, but, instead, may suggest that HAA prepared from IgA-nephritic patients upregulates the activation of G proteins in the plasma membrane.(ABSTRACT TRUNCATED AT 250 WORDS)
Nephron 1995
PMID:Heat-aggregated IgA prepared from patients with IgA nephropathy increases priming of human neutrophils to produce inositol triphosphate following FMet-Leu-Phe stimulation in vitro. 789 78

Previously, we have shown that myocytes from rat portal vein express alpha 1A-adrenoreceptors that couple with a Gq/G11-protein to stimulate phosphoinositide turnover and release of calcium from intracellular stores. The purpose of this study was to investigate the contribution of both alpha 1- and alpha 2-adrenoreceptor subtypes in inducing stimulation of voltage-operated calcium channels. Norepinephrine (a nonselective alpha-adrenoreceptor agonist), phenylephrine (an alpha 1-adrenoreceptor agonist), clonidine, and oxymetazoline (alpha 2-adrenoreceptor agonists) stimulated the calcium channel current by a similar extent. Using subtype-selective antagonists we showed that both alpha 1A- and alpha 2A-adrenoreceptors modulated voltage-operated calcium channels through two distinct transduction pathways. alpha 1A-Adrenoreceptors coupled with a pertussis toxin-insensitive G-protein whereas alpha 2A-adrenoreceptors coupled with a pertussis toxin-sensitive G-protein. Portal vein myocytes expressed G-proteins that were recognized by anti-alpha q/alpha 11, -alpha i(1-2), and -alpha i(3) antibodies. As internal applications of anti-phosphatidylinositol and anti-alpha q/alpha 11 antibodies had no effect on the alpha 2A-adrenoreceptor-induced enhancement of calcium channel current, these findings suggest that phosphatidylinositol hydrolysis and Gq/G11-protein are not involved in the alpha 2A-adrenoreceptor-induced coupling process. A protein kinase C inhibitor, GF 109203X, and a long term (24 h) treatment with phorbol dibutyrate to decrease the activity of protein kinase C blocked the alpha 1A- and alpha 2A-adrenoreceptor-induced stimulation of calcium channels as well as that stimulation induced by phorbol dibutyrate. Moreover, activation of alpha 2A-adrenoreceptors did not induce a significant calcium release from intracellular stores. These data suggest that two distinct G-proteins, probably Gq/G11 and Gi, coupled to alpha 1A- and alpha 2A-adrenoreceptors regulate calcium influx through voltage-operated calcium channels by two different transduction pathways leading to activation of protein kinase C.
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PMID:Both alpha 1A- and alpha 2A-adrenoreceptor subtypes stimulate voltage-operated L-type calcium channels in rat portal vein myocytes. Evidence for two distinct transduction pathways. 796 39

We examined the types of guanine nucleotide-binding regulatory (G) protein subunits in isolated glomeruli, cortices excluding glomeruli and medullas of rat kidneys using bacterial toxin-catalyzed adenosine 5'-diphosphate (ADP) ribosylation and specific immunoblots. ADP ribosylation catalyzed by cholera or pertussis toxin revealed the presence of stimulatory G (Gs) or inhibitory G (Gi) proteins in membranes of the 3 segments of the kidney. Immunoblots further demonstrated the existence of several G-protein subunits, two Gs-protein alpha-subunits (G alpha s: 45 and 52 kD), Gi-protein alpha 1, alpha 2 and alpha 3-subunits (G alpha i1, G alpha i2: 40-41 kD, G alpha i3: 40 kD), bacterial toxin-insensitive G-protein alpha q- and alpha 11-subunits (G alpha q/11: 42 kD) and G-protein beta-subunits (G beta: 35-36 kD), in membranes of the preparations. The predominant subspecies of G alpha s was a 52-kD protein in glomerular membranes and a 45-kD protein in membranes of cortices and medullas. All of the G-protein subunits examined, however, were not detected in cytosolic fractions of glomeruli, cortices and medullas. Thus, we conclude that detectable quantities of several G-protein subunits including the new G-protein subunit, G alpha q/11, are present in membranes of glomeruli, cortices not containing glomeruli and medullas from the rat kidney. Both the existence of G alpha i1 and/or G alpha i2 subunits in glomeruli and the presence of G alpha q/11 subunits in the 3 preparations are new evidence.(ABSTRACT TRUNCATED AT 250 WORDS)
Nephron 1994
PMID:Regional characterization of G-protein subunits in glomeruli, cortices and medullas of the rat kidney. 801 50

Noradrenaline stimulates not only Ca2+ mobilization but also cAMP formation through activation of alpha 1-adrenoceptors in hepatocytes from mature male rats. We examined which subtype(s) of alpha 1-adrenoceptor mediate these signal transduction mechanisms. Treatment of hepatocytes with chloroethylclonidine produced a dose-dependent inhibition of noradrenaline-induced Ca2+ mobilization, involving both transient and sustained components. Chloroethylclonidine also blocked noradrenaline-induced cAMP accumulation. It was observed that prazosin was much more potent than WB4101 (2-(2,6-dimethoxy-phenoxyethyl)aminomethyl-1,4-benzodioxane) in antagonizing noradrenaline-induced Ca2+ mobilization. The same potency order was found in cAMP formation studies. Pretreatment of rats with pertussis toxin did not affect alpha 1-adrenergic responsiveness. Incubations of hepatocytes with tumor-promoting phorbol esters eliminated both Ca2+ mobilization and cAMP accumulation caused by noradrenaline. Our data suggest that in hepatocytes from mature male rats, single alpha 1B-adrenoceptors are linked to cAMP formation as well as Ca2+ mobilization.
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PMID:Alpha 1B-adrenoceptor-mediated stimulation of Ca2+ mobilization and cAMP accumulation in isolated rat hepatocytes. 810 51

We compared the alpha 1-adrenergic receptor subtypes in two neuronal cell lines, SK-N-MC (human neuroepithelioma) and NB41A3 (murine neuroblastoma). 125I-BE 2254 labeled alpha 1-adrenergic receptor binding sites in membranes from both cell lines. Pretreatment with the alpha 1B-selective alkylating agent chloroethylclonidine (CEC) completely eliminated these binding sites in NB41A3 cells but caused only a 50% loss in SK-N-MC cells. Displacement with subtype-selective antagonists suggested that NB41A3 cells express only the alpha 1B subtype, whereas SK-N-MC cells express a pharmacologically heterogeneous receptor population, including both alpha 1A and alpha 1B subtypes. Norepinephrine increased [3H] inositol phosphate formation in both cell lines, but with different sensitivities to pertussis toxin and the presence of extracellular Ca2+. CEC pretreatment eliminated this response in NB41A3 cells but caused a maximal 42% reduction in SK-N-MC cells. Use of subtype-selective antagonists showed that the [3H]inositol phosphate response involved only the alpha 1B subtype in NB41A3 cells but a combination of subtypes in SK-N-MC cells. Norepinephrine induced both transient and sustained increases in intracellular Ca2+ concentrations in both cell lines, as measured with fura-2. CEC pretreatment abolished the Ca2+ response in NB41A3 cells but had little effect in SK-N-MC cells. In SK-N-MC cells the Ca2+ response was potently blocked by alpha 1A-selective antagonists. Chelation of extracellular Ca2+ eliminated the sustained component of the Ca2+ signal in both cell lines. Poly(A)+ RNA from NB41A3, DDT1MF-2, BC3H1, and MDCK-D1 cell lines showed one or more prominent transcripts (2.2-4.2 kilobases) that strongly hybridized to the hamster alpha 1B cDNA probe but not to the bovine alpha 1C or rat alpha 1D cDNA probes. Poly(A)+ RNA from SK-N-MC cells showed multiple transcripts (1.3-5.6 kilobases) that hybridized to both hamster alpha 1B and rat alpha 1D but not bovine alpha 1C cDNA probes. We conclude that NB41A3 cells contain exclusively alpha 1B-adrenergic receptors linked to inositol phosphate formation and mobilization of intracellular Ca2+, whereas at least two alpha 1-adrenergic receptor forms, which resemble the alpha 1A and alpha 1B subtypes, coexist in SK-N-MC cells. The CEC-insensitive alpha 1A-like subtype in SK-N-MC cells is capable of increasing inositol phosphate formation and mobilizing intracellular Ca2+.
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PMID:Comparison of alpha 1-adrenergic receptor subtypes and signal transduction in SK-N-MC and NB41A3 neuronal cell lines. 839 24

1. The effect of noradrenaline and the selective alpha 2-adrenoceptor agonist, azepexole, on tone and intracellular Ca2+ ([Ca2+]i) was examined in human isolated subcutaneous resistance arteries. Isolated arteries were mounted on an isometric myograph and loaded with the Ca2+ indicator, fura-2, for simultaneous measurement of force and [Ca2+]i. 2. High potassium solution (KPSS), noradrenaline and azepexole increased [Ca2+]i and contracted subcutaneous arteries in physiological saline. When extracellular Ca2+ was removed and the calcium chelator, BAPTA, added to the physiological saline (PSSo), responses to noradrenaline were transient and reduced, and responses to azepexole were markedly inhibited. 3. Ryanodine, an agent which interferes with Ca2+ release from intracellular stores, had little effect on contractile responses to KPSS, noradrenaline or azepexole in physiological saline. The response to caffeine in physiological saline was inhibited by ryanodine. In PSSo, ryanodine partially inhibited contractile responses to noradrenaline and azepexole, and completely abolished the response to caffeine. 4. Noradrenaline and azepexole both significantly increased maximum force achieved by cumulative addition of Ca2+ to a Ca(2+)-free depolarizing solution and shifted the calculated relationship between [Ca2+]i and force to the left, suggesting these agents increase the sensitivity of the contractile apparatus to [Ca2+]i. 5. (-)-202 791, a dihydropyridine antagonist of voltage-operated calcium channels partially inhibited both the contractile response and the rise in [Ca2+]i induced by azepexole. Pre-treatment of arteries with pertussis toxin inhibited responses to azepexole, but had no significant effect on tone induced by KPSS or noradrenaline. ETYA, an inhibitor of phospholipase A2, lipoxygenase and cyclo-oxygenase, had no effect on azepexole-induced contraction in the presence of N omega nitro-L-arginine methyl ester.6. Azepexole, a selective alpha2-adrenoceptor agonist, contracts human subcutaneous resistance arteries by a mechanism largely dependent on the influx of extracellular Ca2", probably through voltage-operated calcium channels. This action involves a pertussis toxin-sensitive G protein, possibly Gi.
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PMID:The mechanism of action of alpha 2-adrenoceptors in human isolated subcutaneous resistance arteries. 856 6

Activation of alpha1 adrenergic receptors stimulates mitogenesis in human vascular smooth muscle cells (HVSMCs). To examine signaling pathways by which activation of alpha1 receptors may induce mitogenesis in HVSMCs, we have found that alpha1 receptor stimulated-DNA synthesis and activation of mitogen-activated protein (MAP) kinase are blocked by wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI 3-kinase). To determine directly if activation of alpha1 receptors stimulated PI 3-kinase, in vitro assays of kinase activity were performed in immunocomplexes precipitated by an antibody against the p85 alpha subunit of PI 3-kinase. Noradrenaline stimulated a time- and concentration-dependent activation of PI 3-kinase in the presence of a beta adrenergic receptor antagonist. Noradrenaline-stimulated PI 3-kinase activation was blocked by antagonists of alpha1 receptors and by pertussis toxin, suggesting that alpha1 receptors activate PI 3-kinase via a pertussis toxin-sensitive G protein. Direct activation of protein kinase C by a phorbol ester did not stimulate PI 3-kinase; also, a Ca2+ L-channel blocker did not inhibit noradrenaline-stimulated PI 3-kinase activity. Increased PI 3-kinase activity was detected in both anti-Ras and anti-phosphotyrosine immunoprecipitates from noradrenaline-stimulated HVSMCs. Moreover, noradrenaline stimulated formation of active Ras-GTP complexes. Because blockade of PI 3-kinase by wortmannin inhibited formation of this complex, this result suggests that Ras might be a target of PI 3-kinase. Noradrenaline stimulated tyrosine phosphorylation of the p85 subunit of PI 3-kinase, and a phosphorylated tyrosine protein could be co-immunoprecipitated with anti-p85 of PI 3-kinase. These results demonstrate that stimulation of alpha1 receptors activates PI 3-kinase in HVSMCs and that alpha1 receptor-activated PI 3-kinase is associated with an increase in active Ras-GTP and activation of tyrosine protein phosphorylation. These pathways may contribute to alpha1 receptor-stimulated mitogenic responses including activation of MAP kinase and DNA synthesis in HVSMCs.
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PMID:Alpha1 adrenergic receptors activate phosphatidylinositol 3-kinase in human vascular smooth muscle cells. Role in mitogenesis. 862 43

The release of [3H]inositol phosphates from myo-[3H]inositol-prelabeled LA-N-2 cells was measured in the presence of beta-adrenoceptor, metabotropic glutamate and bombesin agonists. Norepinephrine and isoproterenol increased the formation of [3H]inositol phosphates in a dose-dependent manner, with an EC50 of 100 microM for norepinephrine and an EC50 of 5 microM for isoproterenol. These stimulations were abolished by propranolol, a beta-adrenoceptor antagonist, with an IC50 in the range of 50-55 microM for both norepinephrine and isoproterenol. The stimulation of [3H]inositol phosphate appearance occurred with varying concentrations of trans-1-amino-1,3-cyclopentanedicarboxylic acid (t-ACPD), a metabotropic glutamate receptor agonist. This release of [3H] inositol phosphates was blunted by its antagonist, 2-amino-3-phosphonopropionic acid (AP-3). Bombesin and neuromedin-B, a bombesin-like peptide, also increased the appearance of [3H]inositol phosphates. This was blunted by the antagonist [Tyr4, D-Phe12] bombesin. The appearance of [3H]inositol phosphates stimulated by t-ACPD was coupled through a cholera toxin-sensitive G-protein and the bombesin-stimulated appearance of [3H]inositol phosphates was coupled through a pertussis toxin-sensitive G-protein. The norepinephrine-stimulated appearance of [3H]inositol phosphates was toxin insensitive. The stimulation of the [3H]inositol phosphate appearance by these three agonists was protein kinase and Ca2+ independent.
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PMID:Stimulation of phospholipase C activity by norepinephrine, t-ACPD and bombesin in LA-N-2 cells. 883 35

Cell swelling in Madin-Darby canine kidney (MDCK) cells by reduction of extracellular osmolarity (omission of 70 ad 150 mmol/l mannitol, respectively) leads to the activation of anion of channels and Ca2+ sensitive K+ channels. The K+ channel activation leads to an initial transient hyperpolarization of the cell membrane potential (PD) followed by a sustained depolarization due to activation of anion channels. The present study elucidates the role of intracellular calcium (Ca2+i) in regulatory cell volume decrease (RVD) of MDCK cells. While reduction of extracellular osmolarity by omitting 70 mmol/l mannitol did not lead to a detectable change in Ca2+i, severe cell swelling by omitting 150 mmol/l mannitol led to a transient rise in Ca2+i. PD changes, on the other hand, were not different under either condition. In addition, the response of PD to cell swelling was not altered by treatment of the cells with 12-O-tetradecanoylphorbol-13-acetate diester, pertussis toxin or cholera toxin. In the nominal absence of extracellular Ca2+, reduction of extracellular osmolarity did not lead to an increase in Ca2+i and no initial transient hyperpolarization was observed, whereas addition of 10 mumol/l ATP still led to a significant hyperpolarization. Omission of extracellular Ca2+ was followed by a strong decrease in cell membrane resistance (Rm) due to activation of a depolarizing cation conductance. Subsequent readdition of Ca2+ caused a marked increase in Ca2+i due to Ca2+ influx. This Ca2+ entry was further stimulated by cell swelling. RVD was significantly blunted in the absence of extracellular Ca2+. The results suggest that cell swelling stimulates a Ca2+-permeable pathway in the cell membrane favoring Ca2+ entry into the cell with subsequent activation of Ca2+-sensitive K+ channels.
Nephron 1996
PMID:Calcium entry stimulated by swelling of Madin-Darby canine kidney cells. 888 34

Norepinephrine and the beta-adrenergic receptor agonist, isoproterenol, have been shown to potentiate the amplitude of GABAA receptor-mediated whole-cell current responses in Purkinje cells acutely dissociated from the rat cerebellum. However, the steps leading from the activation of beta-adrenergic receptors to the modulation of GABAA receptor remain to be delineated. This study tested the hypothesis that a sequelae of intracellular intermediaries involving the cyclic AMP second messenger system serves as the subcellular link to promote this heteroreceptor interaction. Exposure to cholera toxin, but not to pertussis toxin, increased the amplitude of GABA-activated current responses in acutely dissociated Purkinje cells. Intracellular dialysis with guanosine 5'-O-(3-thiotriphosphate) also resulted in a time- and dose-dependent augmentation of the response to GABA. while guanosine 5'-O-(2-thiodiphosphate) blocked the norepinephrine-mediated facilitation. A positive modulation of the current response to GABA was observed following intracellular delivery of cyclic AMP or the catalytic subunit of the cyclic AMP-dependent protein kinase. Furthermore, the norepinephrine-induced potentiation of the GABA-activated current response was prevented in the presence of the Rp isomer of cyclic AMP, the regulatory subunit of cyclic AMP-dependent protein kinase and an inhibitor of cyclic AMP-dependent protein kinase. These findings led to the formulation of a working model in which activation of the beta-adrenergic receptor triggers a Gs-protein-mediated transduction cascade in cerebellar Purkinje cells which activates adenylate cyclase, resulting in a rise in intracellular levels of cyclic AMP, increased phosphorylating activity by cyclic AMP-dependent protein kinase and, ultimately, a potentiation of GABAA receptor function.
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PMID:Noradrenergic potentiation of cerebellar Purkinje cell responses to GABA: cyclic AMP as intracellular intermediary. 888 79


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