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)

The components of the polymorphonuclear leukocyte (PMNL) receptor for leukotriene B4 (LTB4) were examined by Sephacryl S-300 exclusion chromatography of PMNL membrane proteins, which were solubilized before and after the binding of [3H] LTB4. When the PMNL membranes were solubilized in 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate (CHAPS) and filtered on Sephacryl S-300 prior to addition of [3H] LTB4, the binding activity was associated with a 65 kD protein. In contrast, the radioactivity of [3H] LTB4 bound to PMNL membranes prior to solubilization was recovered predominantly with a 140 kD protein. When PMNL membranes had been pretreated with pertussis toxin, but not cholera toxin, before the addition of LTB4 and subsequent solubilization, radioactivity was recovered predominantly with the 65 kD protein. The addition of guanylylimidodiphosphate (GMP-PNP), a nonhydrolyzable derivative of guanosine triphosphate (GTP), to PMNL membrane receptors bearing [3H] LTB4 either prior to or after CHAPS solubilization reduced the yield of the 140 kD presumed LTB4 receptor protein-G protein complex. That the maximum specific binding of [35S] guanosine-5'-0-3-thiotriphosphate (GTP-gammaS) to LTB4-binding proteins in the Sephacryl S-300 effluent corresponded to the 140 kD protein supported the presence of a G protein in the LTB4 receptor complex.
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PMID:Ligand-induced formation of the leukotriene B4 receptor-G protein complex of human polymorphonuclear leukocytes. 131 88

1. Actions of histamine on the voltage-dependent Ba2+(Ca2+) currents (IBa, ICa) were investigated using the whole-cell patch-clamp technique on dispersed smooth muscle cells from the rabbit saphenous artery. 2. Histamine (half-maximal dose, EC50 = 530 nM) augmented the IBa evoked by a brief depolarizing pulse (100 ms duration; to +10 mV from a holding potential of -80 mV) in a concentration-dependent manner. The maximum augmentation was obtained with 30 microM-histamine (1.29 times control). This augmentation of IBa was inhibited by the H3-antagonist, thioperamide (Ki = 30 nM, slope of the Schild plot = 1.0), but not by H1- or H2-antagonists (mepyramine or diphenhydramine, or cimetidine, respectively). 3. An H3-agonist, R alpha-methylhistamine (EC50 = 93 nM), also augmented IBa in a concentration-dependent manner at a holding potential of -80 mV and the maximum augmentation (1.25 times control) was obtained with 10 microM. This augmentation was also inhibited by thioperamide, but not by the above H1- and H2- antagonists. 4. Intracellularly applied 500 microM-guanosine 5'-triphosphate (GTP) enhanced, but 1 mM-guanosine 5'-O-(2-thiodiphosphate) (GDP beta S) abolished, the histamine-induced augmentation of IBa. When one of the non-hydrolysable GTP analogues, guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S; greater than 5 microM), guanylyl-imidodiphosphate (GMP-PNP; 200 microM) or guanylyl (beta, gamma-methylene)-diphosphonate (GMP-PCP; 1 mM) was intracellularly applied, the IBa amplitude evoked without the application of histamine was not affected, but the excitatory effect of histamine on IBa was reversed to an inhibition. Pre-treatment with pertussis toxin (PTX: 300 ng/ml and 3 micrograms/ml) did not modify the histamine-induced responses in the absence or presence of GTP gamma S. 5. 4 beta-Phorbol 12,13-dibutylate (PDBu) increased the amplitude of IBa. However, this action of PDBu was not enhanced by the application of GTP (500 microM) in the pipette, but additional application of histamine further increased the amplitude of IBa. Pre-treatment with a potent non-selective protein kinase inhibitor, 1-(5-isoquinolinesulphonyl)-2-methylpiperazine dihydrochloride (H-7; 100 microM), did not modify the histamine-induced current augmentation or inhibition observed in the presence or absence of intracellular GTP gamma S.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Histamine H3-receptor activation augments voltage-dependent Ca2+ current via GTP hydrolysis in rabbit saphenous artery. 131 41

Electrophysiological evidence shows that voltage-dependent calcium channel (VDCC) activity can be regulated by a large number of neurotransmitters. In particular, guanine nucleotide binding regulatory protein (G protein)-mediated inhibitory modulation of the channel activity has been deduced from evidence that GTP analogues and purified G proteins are able to mimic this effect. The G proteins involved are pertussis toxin (PTx) sensitive. The purpose of the present study was to investigate, using biochemical techniques, whether G protein activation modulates the recognition site for omega-conotoxin GVIA (CgTx), a peptide neurotoxin that selectively labels a population of high-threshold VDCC. Undifferentiated and differentiated (1 mM dibutyryl cyclic AMP, 4 days) NG 108-15 cells were used. In both crude cellular extracts specific binding of 125I-CgTx was characterized. Differentiation induced a sixfold increase in the number of binding sites and doubled the KD value. The in vitro addition of guanylylimidodiphosphate (GMP-PNP; a nonhydrolyzable analogue of GTP) to extracts prepared from differentiated cells reduced the 125I-CgTx binding by 48%. This effect, observed in undifferentiated cells as well, was also caused by other triphosphate guanine nucleotides, such as GTP, but not by guanosine 5'-O-(2-thiodiphosphate) or adenine nucleotides. Treatment of the cells with PTx prevented the GMP-PNP effect. Moreover, the results obtained after preincubation with specific antisera raised against the alpha subunits of Gi1-2 and Go suggest that Go is the G protein responsible for the observed effect.
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PMID:G protein modulation of omega-conotoxin binding sites in neuroblastoma x glioma NG 108-15 hybrid cells. 132 Dec 29

Whole-cell patch-clamp recordings were obtained from light-responsive on-bipolar cells in retinal slices of the dogfish. Inclusion of the A-subunit of pertussis toxin in the patch-pipette solution resulted in an increase in inward current and membrane conductance, and a block of light-evoked currents of on-bipolar cells. The opposite effect was obtained with the A-subunit of cholera toxin, which blocked light responses, and induced an outward current and a decrease in membrane conductance. These actions were NAD+ dependent. The results show that the G-protein(s) linking glutamate receptors to a cGMP cascade in on-bipolar cells possess sites which are ADP-ribosylated by pertussis and cholera toxins, with no homology to the adenylate cyclase system but possibly with a homology to transducin. Furthermore, inclusion of H-7, a kinase inhibitor in the patch-pipette solution, or of a non-hydrolysable ATP analogue (AMP-PNP) had no effect on light responses, membrane conductance or dark current of on-bipolar cells, suggesting that the components of this cGMP cascade are unlikely to be regulated by protein kinases.
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PMID:The glutamate-receptor linked cGMP cascade of retinal on-bipolar cells is pertussis and cholera toxin-sensitive. 134 16

The mitogenic effect of extracellular ATP on porcine aortic smooth muscle cells (SMC) was examined. Stimulation of [3H]thymidine incorporation by ATP was dose-dependent; the maximal effect was obtained at 100 microM. ATP acted synergistically with insulin, IGF-1, EGF, PDGF, and various other mitogens. Incorporation of [3H]thymidine was correlated with the fraction of [3H]thymidine-labeled nuclei and changes in cell counts. The stimulation of proliferation was also determined by measurement of cellular DNA using bisbenzamide and by following the increase of mitochondrial dehydrogenase protein. The effect of ATP was not due to hydrolysis to adenosine, which shows synergism with ATP. ATP acted as a competence factor. The mitogenic effect of ATP, but not adenosine, was further increased by lysophosphatidate, phosphatidic acid, or norepinephrine. The inhibitor of adenosine deaminase, EHNA, stimulated the effect of adenosine but not ATP. The adenosine receptor antagonist theophylline depressed adenosine-induced mitogenesis. ADP and the non-hydrolyzable analogue adenosine 5'-[beta, gamma-imido]triphosphate (AMP-PNP) were equally mitogenic. Thus extracellular ATP stimulated mitogenesis of SMC via P2Y purinoceptors. The mechanism of ATP acting as a mitogen in SMC was further explored. Extracellular ATP stimulated the release of [3H]arachidonic acid (AA) and prostaglandin E2 (PGE2) into the medium, and enhanced cAMP accumulation in a dose-dependent fashion similar to ATP-induced [3H]thymidine incorporation. Inhibitors of the arachidonic acid metabolism pathway, quinacrine and indomethacin, partially inhibited the mitogenic effect of ATP but not of adenosine. Pertussis toxin inhibited ATP-stimulated DNA synthesis, AA release, PGE2 formation, and cAMP accumulation. Down-regulation of protein kinase C (PKC) by long-term exposure to phorbol dibutyrate (PDBu) partially prevented stimulation of DNA synthesis and activation of the AA pathway by ATP. The PKC inhibitor, staurosporine, antagonized mitogenesis stimulated by ATP. No synergistic effect was found when PDBu and ATP were added together. Therefore, a dual mechanism, including both arachidonic acid metabolism and PKC, is involved in ATP-mediated mitogenesis in SMC. In addition, ATP acted synergistically with angiotensin II, phospholipase C, serotonin, or carbachol to stimulate DNA synthesis. Finally, the possible physiological significance of ATP as a mitogen in SMC was further studied. The effect of endothelin and heparin, which are released from endothelial cells, on ATP-dependent mitogenesis was investigated. Extracellular ATP acted synergistically with endothelin to stimulate a greater extent of [3H]thymidine incorporation than was seen with PDGF plus endothelin. Heparin, believed to have a regulatory role, partially inhibited the stimulation of DNA synthesis caused both by ATP and PDGF.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Extracellular ATP and ADP stimulate proliferation of porcine aortic smooth muscle cells. 135 98

The present study investigates the effect of G protein activation on dihydropyridine recognition sites in PC12 cell membranes. The addition of a stable analogue of GTP, GMP-PNP, increases the displacement of tritiated PN 200-110 produced by Bay K 8644 without modifying the one produced by nitrendipine. This effect is prevented by Pertussis toxin treatment. Functional studies based on the measurement of intracellular calcium concentrations by means of the fura 2 technique show that Pertussis toxin reduces the ability of Bay K8644 to potentiate the increase of cytosolic calcium elicited by 80 mM K+. The results support the hypothesis that a G protein may modulate the activity of voltage-dependent, dihydropyridine-sensitive calcium channels.
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PMID:Modulation of dihydropyridine-sensitive calcium channels: a role for G proteins. 169 Jun 52

Non-hydrolysable analogues of GTP, such as GTP gamma S and GMP-PNP, have previously been shown to inhibit the formation of constitutive secretory vesicles (CSVs) and immature secretory granules (ISGs) from the trans-Golgi network (TGN). Using a cell-free system, we show here that the formation of these vesicles is also inhibited by [A1F4]-, a compound known to act on trimeric G-proteins. Addition of highly purified G-protein beta gamma subunits stimulated, in a differential manner, the cell-free formation of both CSVs and ISGs. ADP-ribosylation experiments revealed the presence of a pertussis toxin-sensitive G-protein alpha subunit in the TGN. We conclude that trimeric G-proteins regulate the formation of secretory vesicles from the TGN.
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PMID:Trimeric G-proteins of the trans-Golgi network are involved in the formation of constitutive secretory vesicles and immature secretory granules. 175 66

1. Intracellular mechanism(s) for controlling the opening of muscarinic K+ channels in the absence of an applied muscarinic agonist were studied in rabbit atrium by applying the patch clamp technique to isolated single myocytes. 2. In the cell-attached patch configuration, currents due to the activity of both the muscarinic K+ channel and the inward rectifying K+ channel were recorded. However, while the inward rectifying K+ channel currents were observed in only ten patches of 211 examined, spontaneous opening (i.e. in the absence of a muscarinic agonist) of the muscarinic K+ channel currents was observed in all patches examined in these atrial cells. 3. The single-channel currents due to spontaneous opening of muscarinic K+ channels were identified on the basis of their very similar conductance and gating properties to the unitary events which have been recorded when 0.5 microM-acetylcholine is included in the pipette and 10 microM-GTP is present in the internal side of the patch membrane. 4. Although the spontaneous opening of the muscarinic K+ channels disappeared soon after excision of the patch membrane, this type of channel activity reappeared following application of ATP and MgCl2 to the internal side of the torn-off patch, as expected from previous publications. 5. The K+ channel activity induced by the ATP and Mg2+ (measured as the product of the number of channels, N, times the probability of opening, Po) was strongly dependent upon concentration of free Mg2+; it was half-maximal at 2.2 x 10(-4) M [Mg2+]i. However, after the muscarinic K+ channels had been activated by 100 microM-guanosine 5'-O-3-thiotriphosphate (GTP gamma S) together with ATP and Mg2+, an increase in the Mg2+ concentration from 5.5 x 10(-5) to 2 x 10(-3) M failed to enhance this channel activity. 6. Pertussis toxin, which is known to uncouple muscarinic receptors from associated G-proteins (G(i) or G(o)), failed to inhibit the ATP- and Mg(2+)-induced activation of this K+ channel in the absence agonists. 7. In experiments made to test whether the Mg(2+)-ATP requirement results from an obligatory phosphorylation reaction, ATP was replaced with adenylyl-imidodiphosphate (AMP-PNP), an analogue of ATP which is resistant to hydrolysis. This K+ channel activity was not present when ATP was replaced with AMP-PNP.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Regulation of spontaneous opening of muscarinic K+ channels in rabbit atrium. 184 59

We have previously shown that extracellular ATP acts as a mitogen via protein kinase C (PKC)-dependent and independent pathways (Wang, D., Huang, N., Gonzalez, F.A., and Heppel, L.A. Multiple signal transduction pathways lead to extracellular ATP-stimulated mitogenesis in mammalian cells. I. Involvement of protein kinase C-dependent and independent pathways in the mitogenic response of mammalian cells to extracellular ATP. J. Cell. Physiol., 1991). The present aim was to determine if metabolism of arachidonic acid, resulting in prostaglandin E2 (PGE2) synthesis and elevation of cAMP levels, plays a role in mitogenesis mediated by extracellular ATP. Addition of ATP caused a marked enhancement of cyclic AMP accumulation in 3T3, 3T6, and A431 cells. Aminophylline, an antagonist of the adenosine A2 receptor, had no effect on the accumulation of cyclic AMP elicited by ATP, while it inhibited the action of adenosine. The accumulation of cyclic AMP was concentration dependent, which corresponds to the stimulation of DNA synthesis by ATP. The maximal accumulation was achieved after 45 min, with an initial delay period of about 15 min. That the activation of arachidonic acid metabolism contributed to cyclic AMP accumulation and mitogenesis stimulated by ATP in 3T3, 3T6, and A431 cells was supported by the following observations: (a) extracellular ATP stimulated the release of [3H]arachidonic acid and PGE2 into the medium; (b) inhibition of arachidonic acid release by inhibitors of phospholipase A2 blocked PGE2 production, cyclic AMP accumulation, and DNA synthesis activated by ATP, and this inhibition could be reversed by adding exogenous arachidonic acid; (c) cyclooxygenase inhibitors, such as indomethacin and aspirin, diminished the release of PGE2 and blocked cyclic AMP accumulation as well as [3H]thymidine incorporation in response to ATP; (d) PGE2 was able to restore [3H]thymidine incorporation when added together with ATP in the presence of cyclooxygenase inhibitors; (e) pertussis toxin inhibited ATP-stimulated DNA synthesis in a time- and dose-dependent fashion as well as arachidonic acid release and PGE2 formation. Other evidence for involvement of a pertussis toxin-sensitive G protein(s) in ATP-stimulated DNA synthesis as well as in arachidonic acid release is presented. In A431 cells, the enhancement of arachidonic acid and cyclic AMP accumulation by ATP was partially blocked by PKC down-regulation, implying that the activation of PKC may represent an additional pathway in ATP-stimulated metabolism of arachidonic acid. In all of these studies, ADP and AMP-PNP, but not adenosine, were as active as ATP.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Multiple signal transduction pathways lead to extracellular ATP-stimulated mitogenesis in mammalian cells: II. A pathway involving arachidonic acid release, prostaglandin synthesis, and cyclic AMP accumulation. 185 Jul 50

In phagocytes, activation of the respiratory burst by chemoattractants requires ATP and involves a pertussis toxin-sensitive G protein. ATP is also required for the response elicited in permeabilized neutrophils by nonhydrolyzable GTP analogs, indicating that at least one of the ATP-dependent steps lies downstream of the receptor-coupled G protein(s). A respiratory burst can also be produced in a reconstituted cell-free system by addition of arachidonic acid. Most investigators find this response to be independent of ATP, yet stimulated by GTP analogs, implying that the ATP-dependent steps observed in the unbroken cells must precede the guanine nucleotide-requiring event. To resolve this apparent discrepancy, we studied the ATP and guanine nucleotide dependence of the oxidative response elicited by arachidonic acid in electrically permeabilized human neutrophils. Two components of the response were apparent: one was ATP-dependent, the other ATP-independent. The ATP-dependent component was partially inhibited by staurosporine, suggesting involvement of protein kinase C. This kinase signals activation of the NADPH oxidase without intervening G proteins, since stimulation by phorbol ester was unaffected by guanosine 5'-(beta-thio)diphosphate (GDP beta S). Although nonhydrolyzable GTP analogs failed to stimulate the oxidase in the absence of ATP, the ATP-independent response stimulated by arachidonic acid was found to require GTP or one of its analogs and to be inhibited by GDP beta S. The relative potency of the guanine nucleotides to support the arachidonic acid response in the absence of ATP (5'-guanylyl imidodiphosphate (GMP-PNP) greater than or equal to guanosine 5'-(gamma-thio)triphosphate GTP gamma S) greater than or equal to (GTP) differed from their efficacy to stimulate the burst in the presence of ATP (GTP gamma S greater than GMP-PNP much greater than GTP). These observations suggest the involvement of two distinct GTP-binding proteins in oxidase activation: a receptor-coupled, heterotrimeric, pertussis toxin-sensitive G protein, and a second GTP-binding protein(s) located downstream of the ATP-requiring steps, which may lie in close proximity to the NADPH oxidase. This secondary GTP-binding protein could be part of the pathway activated by chemoattractants, but does not mediate stimulation via protein kinase C. Therefore multiple parallel routes may exist for activation of the NADPH oxidase.
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PMID:ATP and guanine nucleotide dependence of neutrophil activation. Evidence for the involvement of two distinct GTP-binding proteins. 216 41


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