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)

Activation of epidermal growth factor (EGF) receptors stimulates inositol phosphate production in rat hepatocytes via a pertussis toxin-sensitive mechanism, suggesting the involvement of a G protein in the process. Since the first event after receptor-G protein interaction is exchange of GTP for GDP on the G protein, the effect of EGF was measured on the initial rates of guanosine 5'-O-(3-[35S]thiotriphosphate) [( 35S]GTP gamma S) association and [alpha-32P]GDP dissociation in rat hepatocyte membranes. The initial rate of [35S]GTP gamma S binding was stimulated by EGF, with a maximal effect observed at 8 nM EGF. EGF also increased the initial rate of [alpha-32P]GDP dissociation. The effect of EGF on [35S]GTP gamma S association was blocked by boiling the peptide for 5 min in 5 mM dithiothreitol or by incubation of the membranes with guanosine 5'-O-(2-thiodiphosphate) (GDP beta S). EGF-stimulated [35S]GTP gamma S binding was completely abolished in hepatocyte membranes prepared from pertussis toxin-treated rats and was inhibited in hepatocyte membranes that were treated directly with the resolved A-subunit of pertussis toxin. The amount of guanine nucleotide binding affected by occupation of the EGF receptor was approximately 6 pmol/mg of membrane protein. Occupation of angiotensin II receptors, which are known to couple to G proteins in hepatic membranes, also stimulated [35S]GTP gamma S association with and [alpha-32P]GDP dissociation from the membranes. The effect of angiotensin II on [alpha-32P]GDP dissociation was blocked by the angiotensin II receptor antagonist [Sar1,Ile8]angiotensin II, demonstrating that the guanine nucleotide binding was receptor-mediated. In A431 human epidermoid carcinoma cells, EGF stimulates inositol lipid breakdown, but the effect is not blocked by treatment of the cells with pertussis toxin. In these cells, EGF had no effect on [35S]GTP gamma S binding. Occupation of the beta-adrenergic receptor in A431 cell membranes with isoproterenol did stimulate [35S] GTP gamma S binding, and the effect could be completely blocked by l-propranolol. These results support the concept that in hepatocyte membranes, EGF receptors interact with a pertussis toxin-sensitive G protein via a mechanism similar to other hormone receptor-G protein interactions, but that in A431 human epidermoid carcinoma cells, EGF may activate phospholipase C via different mechanisms.
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PMID:The epidermal growth factor receptor is coupled to a pertussis toxin-sensitive guanine nucleotide regulatory protein in rat hepatocytes. 164 88

In the present study, we have examined the direct actions of angiotensin II (AII) in rabbit renal brush border membrane (BBM) where binding sites for AII exist. Addition of AII (10(-11)-10(-7) M) was found to stimulate 22Na+ uptake by the isolated BBM vesicles directly. All did not affect the Na(+)-dependent BBM glucose uptake, and the effect of AII on BBM 22Na+ uptake was inhibited by amiloride, suggesting the involvement of Na+/H+ exchange mechanism. BBM proton permeability as assessed by acridine orange quenching was not affected by AII, indicating the direct effect of AII on Na+/H+ antiport system. In search of the signal transduction mechanism, it was found that AII activated BBM phospholipase A2 (PLA) and that BBM contains a 42-kDa guanine nucleotide-binding regulatory protein (G-protein) that underwent pertussis toxin (PTX)-catalyzed ADP-ribosylation. Addition of GTP potentiated, while GDP-beta S or PTX abolished, the effects of AII on BBM PLA and 22Na+ uptake, suggesting the involvement of G-protein in AII's actions. On the other hand, inhibition of PLA by mepacrine prevented AII's effect on BBM 22Na+ uptake, and activation of PLA by mellitin or addition of arachidonic acid similarly enhanced BBM 22Na+ uptake, suggesting the role of PLA activation in mediating AII's effect on BBM 22Na+ uptake. In summary, results of the present study show a direct stimulatory effect of AII on BBM Na+/H+ antiport system, and suggest the presence of a local signal transduction system involving G-protein mediated PLA activation.
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PMID:Angiotensin II directly increases rabbit renal brush-border membrane sodium transport: presence of local signal transduction system. 165 30

The role of guanine nucleotide-binding proteins in the induction of prostacyclin synthesis by stimulated endothelial cells is incompletely understood. We report that sodium fluoride (NaF), a potent activator of cellular guanine nucleotide-binding proteins, affected time- and concentration-dependent generation of prostacyclin (PGI2) by cultured human umbilical vein endothelial cells without evidence of cellular toxicity detected by 51Cr or lactate dehydrogenase release. PGI2 synthesis by NaF-stimulated endothelial cells was associated with increases in arachidonate release, phosphoinositide hydrolysis, generation of inositol phosphates, and accumulation of diacylglycerol. These responses to NaF, as well as alpha-thrombin-mediated responses, were not dependent upon the availability of extracellular free Ca2+ but were associated with the mobilization of stored intracellular Ca2+ detected by the luminescence of the photoprotein aequorin. Neither PGI2 synthesis nor Ca2+ responses following alpha-thrombin or NaF stimulation were inhibited by pretreatment of cells with the islet activating protein from Bordetella pertussis but were significantly attenuated by the G protein inhibitor GDP beta S in permeabilized cells. Our results are compatible with a model wherein NaF directly activates a phosphoinositidase-linked guanine nucleotide regulatory protein, Gp, in human umbilical vein endothelial cell monolayers. This activation results in phosphoinositide hydrolysis, Ca2+ mobilization, arachidonate release, and subsequent functional activation, assessed by PGI2 release. Biologically relevant agonists such as alpha-thrombin may exert their influence on arachidonate metabolism, in part, by promoting receptor-dependent activation of this G protein.
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PMID:Sodium fluoride induces phosphoinositide hydrolysis, Ca2+ mobilization, and prostacyclin synthesis in cultured human endothelium: further evidence for regulation by a pertussis toxin-insensitive guanine nucleotide-binding protein. 165 60

Mouse neuroblastoma x rat glioma hybrid cells (N x G, 108CC15) were used to study the inhibitory effects of the synthetic opioid D-Ala2-D-Leu5-enkephalin (DADLE), somatostatin, adrenaline-alpha 2 and angiotensin II on voltage-dependent Ca(2+)-currents (ICa) using the patch-clamp technique in the whole-cell configuration mode. The inhibitory effects could be abolished by pretreatment of N x G cells with pertussis toxin or intracellular infusion of GDP beta S indicating an involvement of a pertussis toxin sensitive GTP-binding protein (G-protein), presumably Go. The effect of DADLE, the strongest inhibitor of ICa, was studied during dibutyryl cyclic AMP (dBcAMP) induced differentiation. Using omega-conotoxin GVIA (omega-CTX) and methoxyverapamil (D600) as specific Ca(2+)-channel blockers of the N- and L-type Ca(2+)-channels, it was found that in N x G cells DADLE predominantly induces inhibition of T- and N-type Ca(2+)-channels.
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PMID:Inhibitory modulation of fast and slow Ca(2+)-currents in neuroblastoma x glioma cells during differentiation. 165 35

The possible involvement of a GTP-binding protein in the regulation of Ca2+ channels by angiotensin II (Ang II) in vascular muscle cells was investigated by the whole-cell voltage-clamp method. Single cells were freshly isolated from guinea pig portal vein. The pipette solution contained high Cs+ to inhibit K+ currents and thereby isolate the Ca2+ channel current. Ba2+ (2 mM) was in the bath solution as a charge carrier for the Ca2+ channel. Application of Ang II (0.1-100 nM) produced an increase in peak amplitude of the Ba2+ current, with a shift of the current-voltage curve in the negative direction. These effects were inhibited by pretreatment with an antagonist of the Ang II receptor, [Sar1,Ile8]-Ang II. Presence of 0.1 mM GTP in the pipette solution stabilized the Ang II action, but 0.3-1.0 mM GDP-beta-S and 1.0 mM GTP-gamma-S inhibited it. GTP-gamma-S alone produced a slowly progressing increase in the basal (unstimulated) current amplitude. Preincubation of muscle tissues with pertussis toxin (1 micrograms/ml, for up to 6 hours at 36 degrees C) or intracellular application of preactivated pertussis toxin (1 micrograms/ml) plus NAD (1 mM) did not inhibit the Ang II action. Cholera toxin (10 micrograms/ml) also had no effect on the Ang II action. These results suggest that the Ang II stimulation of Ca2+ channels in smooth muscle of guinea pig portal vein may be mediated by a G protein that is insensitive to both pertussis toxin and cholera toxin.
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PMID:Involvement of a GTP-binding protein in stimulating action of angiotensin II on calcium channels in vascular smooth muscle cells. 166 Mar 61

GABA acts as a presynaptic inhibitory transmitter in the spinal cord. In the lamprey, it has recently been shown that it acts in this way at both primary sensory and motor system synapses and is important in the generation of a locomotor rhythm. Both GABAA and GABAB receptors are activated at these sites by GABA released during physiological activity. In some systems, GABAB receptor activation has been shown to lead to modulation of ion channel function indirectly through the action of a pertussis toxin (PTX)-sensitive G-protein. Here we have studied the mechanism of action of the presynaptic GABAB receptor in this system. GABAB receptor activation leads to a decrease in axonal membrane impedance and also to a reduction in the axonal action potential duration. The ionic basis for this response remains unknown, though it is not, unlike the response to GABAA receptor activation, mediated by an increase in conductance to Cl-. The effects of GABAB receptor antagonism with phaclofen are mimicked by pretreatment of the spinal cord with PTX. Because this procedure inactivates certain classes of G-proteins, it seemed likely that the GABAB receptor-mediated effects are initiated via a presynaptic population of PTX-sensitive G-proteins. Experiments in which only presynaptic G-proteins were interfered with indicate that this is so. Stable analogs of GTP and GDP were used to activate permanently or to antagonize, respectively, the GTP binding site in the presynaptic component of these spinal synapses. We conclude that GABAB receptor-mediated synaptic suppression in the spinal cord is caused by GTP binding to presynaptic G-proteins linked to the GABAB receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The involvement of GABAB receptors and coupled G-proteins in spinal GABAergic presynaptic inhibition. 166 May 34

Transducin, the signal coupling protein of retinal rod photoreceptor cells, is one of a family of G proteins that can be inactivated by pertussis toxin. We have investigated the nature of this inactivation in order to determine (1) whether it requires the toxin-catalyzed transfer of ADP-ribose from NAD+ to cysteine-347 of the alpha subunit and (2) whether it involves locking the alpha subunit in the inactive conformation characteristic of its GDP-bound state, or is limited to disruption of binding to photoexcited rhodopsin (R*). Our results indicate that all observed effects of pertussis toxin treatment, including a shift in the electrophoretic mobility of transducin's alpha subunit and functional inactivation, require NAD+ and that the appearance of the shift parallels incorporation of ADP-ribose. We have also found that, apart from interactions with photoexcited rhodopsin, the functional properties of ADP-ribosylated transducin are essentially the same as those of unmodified transducin. Normal spontaneous nucleotide exchange kinetics and the ability to activate cGMP phosphodiesterase are preserved following quantitative ADP-ribosylation, as are the abilities to hydrolyze GTP, to bind to a dye affinity column, and to display enhanced fluorescence upon addition of Al3+ and F-. Thus, ADP-ribosylation merely blocks catalysis of transducin nucleotide exchange by R* and does not lock transducin in an inactive state.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nucleotide exchange and cGMP phosphodiesterase activation by pertussis toxin inactivated transducin. 166 Nov 43

Injection of rats with a single dose of epidermal growth factor (EGF) or isoproterenol increased parotid gland acinar cell levels of cyclic AMP (cAMP) significantly above control basal concentrations (34, 177 and 11.5 pmol/g tissue/100 g body weight, respectively). Following a chronic regimen of isoproterenol (3 days), EGF, bovine galactosyltransferase (Gal Tase, EC 2.4.1.22) and isoproterenol increased cAMP levels, albeit to a lower level than observed for the single dose (21, 17 and 51 pmol, respectively). Using isolated parotid gland membranes, EGF and bovine galactosyltransferase also stimulated adenylate cyclase (EC 2.7.4.3) activity in a concentration-dependent manner. Introduction of the beta-adrenergic receptor antagonist propranolol blocked isoproterenol-stimulated adenylate cyclase activity and cAMP accumulation, but not that observed with EGF or the transferase treatment. Growth factor-stimulated adenylate cyclase activity required the presence of the guanosine triphosphate (GTP) analogue, guanyl-5'-imidodiphosphate (p[NH]ppG), while cAMP accumulation could additionally be blocked by introducing the GDP analog, guanosine 5'[beta-thio]diphosphate (GDP[S]). The ability of EGF to activate adenylate cyclase was not affected by pretreatment of acinar cell membranes with pertussis toxin, whereas pretreatment with cholera toxin eliminated EGF-stimulated cyclase activity. The experimental results presented here expand to the parotid gland our knowledge of the ability of EGF to stimulate the cAMP second messenger signalling pathway via a G-binding regulatory protein, by a mechanism independent of beta-adrenergic receptor activation.
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PMID:Epidermal growth factor activation of rat parotid gland adenylate cyclase and mediation by a GTP-binding regulatory protein. 166 11

The release of arachidonic acid from cellular phospholipids and its subsequent conversion to eicosanoids is the common early response of skin keratinocytes to a wide variety of exogenous or endogenous agonists including irritant skin mitogens such as the phorbol ester, 4 beta-phorbol 12-myristate 13-acetate (PMA) or the inflammatory peptide bradykinin. In mouse keratinocytes labeled with [14C]arachidonic acid, both PMA and bradykinin induced the release of the fatty acid in a dose-dependent and time-dependent manner. Three lines of evidence indicate phospholipase A2 activity to be involved in arachidonic acid release: (a) its inhibition by mepacrine, (b) the concomitant generation of lysophosphatidylcholine from [3H]choline-labeled cells and (c) an increase in arachidonic acid release from 14C-labeled phosphatidylcholine in particulate fractions from PMA-treated and bradykinin-treated keratinocytes. Inhibition or down regulation of protein kinase C (PKC) led to a suppression of PMA-induced but not bradykinin-induced arachidonic acid release, indicating a critical involvement of this kinase in phorbol-ester-induced activation of epidermal phospholipase A2 activity. Bradykinin-induced activation of phospholipase A2 was however, shown to be mediated by specific B2 receptors coupled to GTP-binding proteins (G protein). In support of this mechanism it was demonstrated that the bradykinin-induced phospholipase A2 activity was increased in the presence of non-hydrolysable GTP but decreased upon addition of non-hydrolysable GDP analogues. Moreover, cholera toxin stimulated both basal and bradykinin-induced phospholipase A2 activity in a cAMP-independent manner, whereas pertussis toxin was found to be inactive in this respect. The data suggest that epidermal phospholipase A2 activity can be stimulated by bradykinin via a B2 receptor-G-protein-dependent pathway, which is independent of PKC and a PKC-dependent pathway which is activated by phorbol esters such as PMA.
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PMID:Activation of a keratinocyte phospholipase A2 by bradykinin and 4 beta-phorbol 12-myristate 13-acetate. Evidence for a receptor-GTP-binding protein versus a protein-kinase-C mediated mechanism. 166 19

The release of arachidonic acid from mouse peritoneal and S49 cells induced by delta 1-tetrahydrocannabinol was found to be altered by prior exposure of the cells to either pertussis toxin or cholera toxin. The stable analogs of GTP and GDP, GTP-gamma-S and GDP-beta-S, were also effective in changing the extent of arachidonate release in saponin-treated cells. GDP-beta-S essentially abolished the THC response, while GTP-gamma-S showed effects mainly on vehicle-treated cells. The cataleptic action of THC in intact mice which is mediated by eicosanoids was also attenuated by pertussis toxin pretreatment. It is suggested that the THC receptor is coupled to phospholipases through one or more G-proteins and that adenylate cyclase probably does not have a role in this mechanism.
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PMID:G-protein mediation of cannabinoid-induced phospholipase activation. 166 19


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