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 polymorphonuclear leukocytes (PMN) express receptors for complement (C) C3b and C3bi termed CR1 and CR3, respectively. The addition of PMA or fMLP to PMN enhances the capacity of these receptors to promote binding of C3b- and C3bi-coated erythrocytes. fMLP-dependent increase of the binding of these ligand-coated erythrocytes was completely abolished by prior exposure of the PMN to pertussis toxin (IAP). GTP-binding protein (Gi alpha) was ADP-ribosylated and dysfunctional by this treatment. On the other hand, PMA-dependent binding of these ligands, as well as control binding, was inhibited only slightly, if at all, by the IAP treatment. The levels of C receptor expression on cell surface were determined by flow cytometry using monoclonal antibody against CR1 and those against the alpha and beta chains of CR3 (CR3 is composed of alpha and beta chain). Upon exposure of PMN to the chemotactic factor or PMA, or upon incubation of the cells at 37 degrees C, the surface expression of CR1 and CR3 alpha was increased. IAP also blocked an fMLP-induced increase of CR1 and CR3 alpha, but did not block the temperature- or PMA-dependent increase of these receptors. Opsonized zymosan (SOZ), another ligand for CR3, also led to an increase of both CR1 and CR3 alpha. Neither PMA nor SOZ brought about an increase of the surface expression of CR3 beta, but fMLP caused a slight increase of CR3 beta in an IAP-sensitive manner. Based on the IAP-sensitivity of the receptor expression, therefore, it appears that at least two separate mechanisms are operative in the control of C receptors. In addition, the alpha and beta chains of CR3 are regulated independently. The present data offer evidence suggesting that C receptor functions are in part regulated through a GTP-binding protein via modulation of their surface expression.
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PMID:Involvement of the pertussis toxin-sensitive GTP-binding protein in regulation of expression and function of granulocyte complement receptor type 1 and type 3. 819 Jan 26

1. The effects of acetylcholine (ACh) on granule cells freshly dissociated from rat dentate gyrus (DG) were studied using the nystatin perforated patch technique. This method allowed us to study ACh-induced currents (IACh) under voltage clamp without "run-down" of the ACh response. In some experiments, we used the conventional whole-cell method for intracellular application of drugs not permeable to cell membrane. 2. At a holding potential of -40 mV, ACh induced an outward current. The amplitude of IACh increased in a sigmoidal fashion with increasing ACh concentration. The half-maximal response and the Hill coefficient determined from the relation between ACh concentration and response were 4.98 x 10(-7) M and 1.70, respectively. 3. The reversal potential of IACh was close to the K+ equilibrium potential. The IACh was accompanied by an enhancement of the K+ current. 4. Muscarine and McN-A-343 mimicked the ACh response, whereas oxotremorine induced no response. 5. Muscarinic antagonists reversibly suppressed the IACh (10(-5) M) in a concentration-dependent manner, where the values of half-inhibition concentration (IC50) were 1.03 x 10(-6) M for pirenzepine and 2.21 x 10(-5) M for AF-DX-116. 6. Intracellular perfusion with GDP-beta S suppressed the IACh greatly. The IACh persisted in the neurons pretreated with an external solution containing pertussis toxin (IAP) for 18 h. 7. In the neurons perfused with Ca(2+)-free external solution containing 2 mM ethylene glycol-O,O'-bis (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid and 10 mM Mg2+, the first application of ACh induced the IACh with an amplitude similar to that in the standard solution.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Muscarinic receptor activation of potassium channels in rat dentate gyrus neurons. 828 13

Effects of an adenosine A1-receptor agonist and antagonist were determined in pertussis toxin (IAP)-treated and non-treated rats. (-)-N6-(2-phenylisopropyl) adenosine, an adenosine A1-agonist, reduced the urine volume and sodium excretion without decreasing the glomerular filtration rate at 0.1 mg/kg (p.o.) in both IAP-treated and non-treated rats. Diuretic effects of KW-3902 (8-(noradamantan-3-yl)-1,3-dipropylxanthine) and 8-cyclopentyl-1,3-dipropylxanthine, adenosine A1-receptor antagonists, were not affected by pretreatment with IAP. These results suggest that endogenous adenosine may induce antidiuretic effects by accelerating the reabsorption of water and sodium at tubular sites via an IAP-insensitive mechanism, and that the diuretic effects of the adenosine A1-receptor antagonist may result from inhibiting this action of endogenous adenosine.
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PMID:Effects of adenosine A1-agonist and -antagonist on urinary volume and Na excretion in IAP-treated and non-treated rats. 828 37

ADP-ribose moiety containing digoxigenin was transferred by pertussis toxin (IAP) to the alpha subunit of Gi (Gi alpha) from digoxigenin-conjugated NAD (DIG-NAD) in a beta gamma subunit-dependent manner. ADP-ribosylation of Gi alpha with DIG-NAD plus IAP was inhibited by native NAD. These results indicate that non-radiolabeled DIG-NAD also serves as the substrate for IAP-catalyzed ADP-ribosylation of G proteins. Using DIG-NAD and fluorescein isothiocyanate-labeled anti-digoxigenin antibody, IAP-sensitive G protein(s) was found to be exist in nuclei as well as plasma membranes of rat liver and HeLa cells. Thus, DIG-NAD is useful to identify pertussis toxin-substrate G proteins.
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PMID:Pertussis toxin-catalyzed ADP-ribosylation of GTP-binding proteins with digoxigenin-conjugated NAD. Identification of the proteins in plasma membranes and nuclei. 830 91

KW-3902 [8-(noradamantan-3-yl)-1,3-dipropylxanthine] is a novel potent and selective adenosine A1-receptor antagonist. In anesthetized rats, KW-3902 (0.1 and 1 mg/kg p.o.) antagonized the 5'-N-ethylcarboxamidoadenosine (NECA) induced bradycardic response, which is thought to be mediated via adenosine A1-receptors. However, the hypotensive response to NECA, which is predominantly due to adenosine A2-receptor activation, was not affected by KW-3902. Diuretic and renal protective effects of KW-3902 were investigated in normal and pertussis toxin (IAP; 10 micrograms/kg i.v.)-treated rats. KW-3902 (0.001-1 mg/kg p.o.) caused significant increases of urine volume and sodium excretion with little change of potassium excretion in saline-loaded normal rats. In anesthetized normal rats, KW-3902 (0.01 and 0.1 mg/kg i.v.) caused significant diuresis and natriuresis with no change in renal plasma flow and glomerular filtration rate. These findings suggest that KW-3902 caused the diuretic effect not by the change in the renal hemodynamics, but by the inhibition of water and sodium reabsorption in tubular sites. KW-3902 (0.01-1 mg/kg p.o.) significantly attenuated increases of serum creatinine and urea nitrogen and renal tubular damage in glycerol-induced acute renal failure rats. Neither diuretic nor renal protective effects of KW-3902 were affected by pretreatment of rats with IAP, which totally abolished the bradycardic response to NECA. These results are compatible with the hypothesis that diuretic and renal protective effects by adenosine A1-receptor blockade are mediated via IAP-insensitive mechanism.
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PMID:Diuretic and renal protective effects of 8-(noradamantan-3-yl)-1,3-dipropylxanthine (KW-3902), a novel adenosine A1-receptor antagonist, via pertussis toxin insensitive mechanism. 833 58

1. We investigated the mechanism of signal transduction during the effect of muscarinic receptor stimulation on Ca2+ transients, tension, Ca2+ sensitivity and the cross-bridge cycling rate (CCR). 2. Membrane-permeable derivatives of cyclic GMP (8-bromo-cyclic GMP and dibutyryl cyclic GMP) did not cause any significant changes in the peaks of Ca2+ transients and tension and the time courses of either signal modulated by isoprenaline (Iso) (0.1 microM). 3. Nitroprusside (0.1-1 mM) likewise did not change the peaks or the time courses of Ca2+ transients and tension in the Iso-treated preparations. 4. In papillary muscles excised from ferrets treated with pertussis toxin (islet-activating protein, IAP), which is known to abolish the function of GTP-binding proteins (Gi, Go and Gt), similar changes in Ca2+ transients and tension produced by treatment with Iso (0.1 microM) were noted as in non-IAP-treated preparations. However, no effects of acetylcholine (ACh; 1 microM) on either signal were observed. 5. The relation between [Ca2+]i and tension measured during the steady state of tetanic contraction was shifted to the right by Iso (0.1 microM), and cyclic GMP derivatives (1 mM) did not change the altered relation. In the IAP-treated preparations, ACh (1 microM) did not influence the relation altered by Iso (0.1 microM). 6. Cyclic GMP derivatives (1 mM) did not alter the Iso (0.1 microM)-increased CCR measured by perturbation analysis. ACh (1 microM) did not restore the Iso-increased CCR in the IAP-treated preparations. 7. These results suggest that signal transduction in muscarinic receptor stimulation is primarily mediated by inhibition of adenylate cyclase via IAP-sensitive GTP-binding proteins, and that cyclic GMP does not play an important role in the effect of muscarinic receptor stimulation on Ca2+ transients, tension, Ca2+ sensitivity or CCR.
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PMID:Mechanism of the effects of acetylcholine on the contractile properties and Ca2+ transients in ferret ventricular muscles. 839 24

In order to study the activation mechanism of heterotrimeric G-proteins by agonist-liganded receptors, GTP gamma S binding to membranes was measured in rat adenohypophyseal cells after addition of dopamine (DA) or vasoactive intestinal peptide (VIP), which, respectively, inhibit and activate pituitary adenylyl cyclase. G-protein subunit present in anterior pituitary cells was characterized by either ADP-ribosylation catalysed by Bordetella pertussis and cholera toxins or by immunoblot using specific antisera. Binding of GTP gamma S was found to depend upon GTP gamma S and Mg2+ concentrations; it was sensitive to pretreatment of the cells with cholera and Bordetella pertussis toxins (IAP). DA increased binding of the nucleotide. Paradoxically, VIP decreased the rate of GTP gamma S binding; the effect was suppressed by prior treatment of the cells with either cholera toxin or IAP. VIP also increased [33P]ADPribose incorporation in Gi/Go-proteins catalysed by IAP. Forskolin was also able to decrease GTP gamma S binding, thus suggesting that the binding of forskolin with the adenylyl cyclase catalytic unit might activate Gs proteins through an increased interaction between Gs and adenylyl cyclase. Taken together, these results suggest that VIP, as well as forskolin, may both accelerate the activation of Gs and suppress the inhibitory effect of activated Gi/Go-proteins. Interactions between Gs and Gi/Go subunits mediated by beta gamma and/or adenylyl cyclase might thus result in a kinetic coupling of transduction pathways involving distinct G-proteins.
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PMID:Vip-induced cross-talk between G-proteins in membranes from rat anterior pituitary cells. 849 23

In the present study, we investigated the mechanism of phenylephrine (alpha-1-adrenergic receptor agonist)-induced arachidonic acid release in Japanese white rabbit aortic smooth muscle cells (SMC). When introduced into permeabilized smooth muscle cells, guanosine S-[gamma-thio] triphosphate (GTPgamma S), which activates GTP-binding proteins (G proteins), stimulated arachidonic acid (AA) release. Neomycin, an inhibitor of phosphoinositide (PI) turnover, was almost without effect on GTP[gamma S] stimulated AA release. In addition, pertussis toxin (PT) partially inhibited phenylephrine-stimulated AA release, suggesting that IAP (Islet activating protein)-sensitive G proteins mediate this process. Phenylephrine-stimulated AA release was also inhibited by decreased extracellular calcium and aristolochic acid, suggesting a role for a phospholipase A2 (PLA2). Next PLA2 is reported to be a substrate for mitogen-activated protein (MAP) kinase. We examined the effect of phenylephrine on MAP kinase and c-jun N-terminal kinase (JNK) phosphorylation. Phenylephrine didn't induce phosphorylation of MAP kinase, but did induce phosphorylation of JNK. In addition, cells which were pretreated with PT inhibited the phosphorylation of JNK. These results suggest that IAP-sensitive G protein is involved in the coupling between alpha1-adrenergic receptor (AR) and PLA2 in cultured rabbit aortic SMCs, and that the alpha1-AR-induced AA release is mediated by JNK.
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PMID:alpha-1-Adrenergic receptor stimulation causes arachidonic acid release through pertussis toxin-sensitive GTP-binding protein and JNK activation in rabbit aortic smooth muscle cells. 860 77

The elucidation for the mechanism of receptor-mediated signal transduction has been the aim of our extensive studies. Cyclic AMP, which was controlled by membrane adenylyl cyclase, was an intracellular signal (the first second messenger in cells proposed by Sutherland) given by hormones and neurotransmitters. The GTP-binding (G) proteins play an important role in communication between membrane receptors and the adenylyl cyclase catalytic unit. One (Gs) of the G proteins is involved in the activation, while the other (Gi) is involved in the inhibition of adenylyl cyclase. Islet-activating protein (IAP, pertussis toxin, PTX) catalyses the transfer of the ADP-ribose moiety of NAD to the alpha subunit of Gi, resulting in a complete loss of the Gi functions. In some cases, arachidonic acid (AA) regulates cell functions as a second messenger. AA serves as a precursor to a number of biologically active lipids including prostaglandins and leukotrienes. Activation of cell surface receptors of many cell types results in the release of AA from membrane phospholipids by phospholipase A2 (PLA2). A new family of PLA2 has been discovered in the cytosol of various cells. The activation of receptor-mediated AA release by cytosolic PLA2 was also regulated by PTX-sensitive G proteins. PTX treatment inhibited cell growth of fibroblasts by serum and growth factors. G proteins have been involved in receptor-receptor interactions in neuronal cells. These findings suggest the regulatory roles of cell surface receptors-coupled G proteins in signal transductions and cell functions.
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PMID:[Receptor-mediated signal transduction]. 870 6

Treatment of rat parotid tissues with 1 microM isoproterenol (IPR) for 10 min caused a 60% decrease in pertussis toxin (IAP)-catalyzed ADP-ribosylation of Gi alpha and resulted in supersensitivity of amylase secretion from the tissues. However, conversely, IPR treatment for 30 min caused a 40% increase in IAP-catalyzed ADP-ribosylation of Gi alpha, coupled with desensitization of amylase secretion. No changes in Gs function were observed in IPR-induced phenomena. Pretreatment with okadaic acid induced enhancement of the supersensitivity of amylase secretion and disappearance of the desensitization. These phenomena were accompanied with decreases in IAP-catalyzed ADP-ribosylation of Gi alpha. IPR treatment for 30 min caused a 50% decrease in phosphorylation of Gi2 alpha immunoprecipitated with anti-G protein antiserum (AS/7) from [32P]Pi-labeled cells, but such treatment for 10 min caused a 40% increase in phosphorylation in the cells pretreated with okadaic acid. Phosphorylation and dephosphorylation of immunoprecipitates with AS/7 by protein kinase A (PKA) and alkaline phosphatase caused decreases and increases in IAP-catalyzed ADP-ribosylation, respectively, indicating the presence of PKA-mediated phosphorylation sites on Gi2 alpha. Thus, the control of the phosphorylation of Gi2 alpha is of importance and relevance in the regulation of biological processes and cellular responses.
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PMID:Regulation of phosphorylation of Gi2 alpha protein controls the secretory response to isoproterenol in rat parotid tissues. 878 62


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