UMLS:C0043167 - FACTA Search

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Query: UMLS:C0043167 (pertussis)
19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

These studies provide evidence that binding of HDL3 to the HDL receptor stimulates translocation and efflux of intracellular cholesterol through mechanisms involving the activation of protein kinase C. This conclusion is supported by data demonstrating that HDL is able to increase cell diacylglycerol levels and activate protein kinase C. Sphingosine, a protein kinase C inhibitor, was able to inhibit HDL3-mediated cholesterol translocation and efflux, further suggesting a role for protein kinase C in HDL receptor-dependent cholesterol efflux. Inhibition of HDL-mediated diacylglycerol formation by pertussis toxin suggests the possible involvement of a G protein-activated phospholipase. Further studies are needed to understand how activation of protein kinase C promotes cholesterol translocation and to identify the target proteins for protein kinase C phosphorylation.
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PMID:Role of the protein kinase C signaling pathway in high-density lipoprotein receptor-mediated efflux of intracellular cholesterol. 166 90

We have shown previously that exposure of a non-transformed continuous line of rat liver epithelial (WB) cells to epidermal growth factor (EGF), adrenaline, angiotensin II or [Arg8]vasopressin results in an accumulation of the inositol phosphates InsP1, InsP2 and InsP3 [Hepler, Earp & Harden (1988) J. Biol. Chem. 263, 7610-7619]. Studies were carried out with WB cells to determine whether the EGF receptor and other, non-tyrosine kinase, hormone receptors stimulate phosphoinositide hydrolysis by common, overlapping or separate pathways. The time courses for accumulation of inositol phosphates in response to angiotensin II and EGF were markedly different. Whereas angiotensin II stimulated a very rapid accumulation of inositol phosphates (maximal by 30 s), increases in the levels of inositol phosphates in response to EGF were measurable only following a 30 s lag period; maximal levels were attained by 7-8 min. Chelation of extracellular Ca2+ with EGTA did not modify this relative difference between angiotensin II and EGF in the time required to attain maximal phospholipase C activation. Under experimental conditions in which agonist-induced desensitization no longer occurred in these cells, the inositol phosphate responses to EGF and angiotensin II were additive, whereas those to angiotensin II and [Arg8]vasopressin were not additive. In crude WB lysates, angiotensin II, [Arg8]vasopressin and adrenaline each stimulated inositol phosphate formation in a guanine-nucleotide-dependent manner. In contrast, EGF failed to stimulate inositol phosphate formation in WB lysates in the presence or absence of guanosine 5'-[gamma-thio]triphosphate (GTP[S]), even though EGF retained the capacity to bind to and stimulate tyrosine phosphorylation of its own receptor. Pertussis toxin, at concentrations that fully ADP-ribosylate and functionally inactivate the inhibitory guanine-nucleotide regulatory protein of adenylate cyclase (Gi), had no effect on the capacity of EGF or hormones to stimulate inositol phosphate accumulation. In intact WB cells, the capacity of EGF, but not angiotensin II, to stimulate inositol phosphate accumulation was correlated with its capacity to stimulate tyrosine phosphorylation of the 148 kDa isoenzyme of phospholipase C. Taken together, these findings suggest that, whereas angiotensin II, [Arg8]vasopressin and alpha 1-adrenergic receptors are linked to activation of one or more phospholipase(s) C by an unidentified G-protein(s), the EGF receptor stimulates phosphoinositide hydrolysis by a different pathway, perhaps as a result of its capacity to stimulate tyrosine phosphorylation of phospholipase C-gamma.
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PMID:Evidence that the epidermal growth factor receptor and non-tyrosine kinase hormone receptors stimulate phosphoinositide hydrolysis by independent pathways. 169 55

Mastoparan, a tetradecapeptide purified from wasp venom, stimulates insulin and glucagon release by rat pancreatic islets in a dose-related manner. In perifusion experiments, mastoparan produces monophasic hormone release, which ceases within 10 min of removal of the peptide. After exposure of the isles to mastoparan, glucose-induced insulin release is clearly retained. In incubation experiments, mastoparan-induced insulin release is greatly blocked by pretreatment of the islets with pertussis toxin or neomycin (inhibitor of phosphoinositide turnover) or by lowering the ambient temperature to 17 C. Pretreatment of the islets with nifedipine (calcium channel blocker), H-7 (inhibitor of A- and C-kinase), somatostatin, or divalent cation-free medium does not affect the response to mastoparan. Pretreatment with parabromophenacylbromide (phospholipase-A2 inhibitor) does not block the response induced by a high concentration of (58 microM) mastoparan. The peptide does not stimulate insulin synthesis during 30 min of incubation. Mastoparan raises the cytosolic free Ca2+ concentration, measured by fura-2, in isolated islet cells at normal (1.9 mM) and very low (6.5 microM) extracellular Ca2+ concentrations. Intravenous administration of mastoparan in rats causes a significant elevation of both insulin and glucagon. Together with the previous data, we conclude that mastoparan stimulates islet hormone release through a temperature-dependent process mediated by pertussis toxin-sensitive GTP-binding protein(s). Activation of phospholipase-C and liberation of intracellular Ca2+ are likely to be coupled to exocytosis. Ca2+ influx through the Ca2+ channel and protein kinase-A and -C appear not to be involved in mastoparan's hormone-releasing action. Phospholipase-A2 may be involved in the hormone release induced by low, but not high, concentrations of the peptide.
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PMID:Mastoparan-induced hormone release from rat pancreatic islets. 172 98

Triethyl lead chloride (Et3PbCl) was found to induce a shift of fatty acids from membrane phospholipids to triacylglycerols in the human promyelocytic leukemia cell line HL-60. High concentrations of Et3PbCl (greater than 10 microM) caused a substantial liberation of [14C]arachidonic acid within 10 to 20 min in dimethyl sulfoxide-differentiated cells, comparable to the effect of the calcium ionophore A23187 (10 microM). Following liberation of arachidonic acid, its metabolites could be detected. Prolongation of the incubation time and reduction of Et3PbCl concentration resulted in a shift of fatty acids from phospholipids to triacylglycerols. Deacylation of phospholipids and reacylation into phospholipids and triacylglycerols were in equilibrium when the cells were treated with Et3PbCl at concentrations of less than or equal to 10 microM for 5 hr or less than or equal to 1 microM for 24 hr; no increase of free fatty acids could be observed, and the loss of fatty acids within the phospholipids was equivalent to the increase of fatty acid content within the triacylglycerols. Moreover, under these conditions, no loss of viability was seen after 24 hr, as compared with untreated differentiated cells. This concentration- and time-dependent effect of Et3PbCl might be due to a stimulated liberation of fatty acids via phospholipase A2, because this stimulation could be totally prevented by the phospholipase inhibitors quinacrine and p-bromophenacylbromide. Additionally, pretreatment of differentiated HL-60 cells with pertussis toxin resulted in a drastic reduction of [14C]arachidonic acid liberation when cells were stimulated with Et3PbCl. These results suggest the involvement of a pertussis toxin-sensitive GTP-binding protein and of a signal transduction mechanism during stimulated fatty acid release; release does not seem to be via a direct stimulation of phospholipase activity by the lead compound.
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PMID:Directed shift of fatty acids from phospholipids to triacylglycerols in HL-60 cells induced by nanomolar concentrations of triethyl lead chloride: involvement of a pertussis toxin-sensitive pathway. 190 39

We have previously shown that dopamine-evoked inhibition of corticosteroid production from adrenocortical cells is mediated through a decrease in prostaglandin biosynthesis. Since the catecholamine did not alter the stimulatory effect of arachidonic acid, it was proposed that dopamine may inhibit the formation of arachidonate from glycerophospholipids. To test this hypothesis, the effect of dopamine on phosphoinositol lipid metabolism was investigated in frog interrenal (adrenal) tissue. In [3H]myo-inositol-prelabeled frog interrenal slices, a short pulse of dopamine (50 microM) induced a biphasic effect on inositol phosphate production: a transient (1-min) increase, followed by a sustained inhibition. Concurrently, dopamine induced a transient reduction followed by a sustained increase in polyphosphoinositides. A 10-min pulse of the D2 dopamine receptor agonist apomorphine (50 microM) elicited a significant inhibition of basal levels of inositol phosphates (tris-, bis-, and mono-), and an increase in plasma membrane phosphoinositol lipid contents. The inhibitory effect of dopamine on inositol phosphate formation and corticosteroid release was abolished by a 24-h incubation of interrenal slices with pertussis toxin. In [3H]arachidonic acid-prelabeled interrenal slices, dopamine also decreased diacylglycerol (DG) and arachidonic acid (AA) concentrations. A delay of 1 min was observed between inhibition of DG and arachidonate, suggesting that AA is probably generated from DG. We conclude that in the adrenal cortex, activation of dopamine D2 receptors is coupled to a phosphoinositide-specific phospholipase-C mediated via a pertussis toxin-sensitive G-protein. Taken together, our data indicate that inhibition of inositol phosphate and AA formation is one of the mechanisms by which dopamine controls corticosteroid production by adrenocortical cells.
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PMID:Dopamine inhibits inositol phosphate production, arachidonic acid formation, and corticosteroid release by frog adrenal gland through a pertussis toxin-sensitive G-protein. 190 70

The regulation of prostacyclin (PGI2) synthesis by cultured human umbilical vein endothelium (HUVEC) was investigated. HUVEC monolayer generation of PGI2 was monitored by RIA of 6-keto PGF1 alpha and dose-dependent increases observed with human alpha- and gamma-thrombins, histamine, or arachidonate. Alpha thrombin (10 nM) produced levels of 6-keto PGF1 alpha approximating responses with 1 microM gamma-thrombin, 5 microM arachidonate, or 10 microM histamine. Diisopropyl phosphorofluoridate-inactivated alpha-thrombin did not stimulate PGI2 release, demonstrating that catalytic activity was required for thrombin-stimulated PGI2 release. Sodium fluoride (NaF), at concentrations known to activate guanine nucleotide regulatory proteins (G proteins), directly stimulated HUVEC PGI2 synthesis in a dose-dependent and time-dependent manner (20 mM NaF, 4.4 +/- 0.5-fold increase at 10 min, 11.9 +/- 1.5-fold increase at 30 min). Neither alpha-thrombin nor NaF-stimulated PGI2 release was dependent upon the availability of extracellular Ca++). The hypothesis that G proteins are involved in agonist-stimulated PGI2 synthesis was further supported by studies using digitonin-permeabilized HUVEC monolayers challenged with another G protein activator, guanosine 5'-0-3-thiotrisphosphate (GTP gamma S), which effected significant dose-dependent increases in PGI2 synthesis compared with control levels of 6-keto PGF1 alpha. In contrast, the G-protein inhibitor GDP beta S, (guanosine 5'-0-2-thiodiphosphate), attenuated alpha-thrombin-mediated prostaglandin generation. Treatment of HUVEC monolayers with pertussis toxin (1 microgram/ml) did not inhibit the PGI2 synthesis stimulated by either alpha-thrombin, NaF, or histamine but catalyzed the ADP ribosylation of a 40 kDa membrane protein which cross-reacted with antisera against a synthetic peptide corresponding to an amino acid sequence common to the alpha-subunit of other G-proteins. Preincubation of HUVEC microsomal membranes with alpha-thrombin diminished pertussis toxin-catalyzed ADP ribosylation in a time-dependent manner. These data suggest that thrombin stimulation of PGI2 synthesis by HUVEC monolayers requires the catalytically functional enzyme and further suggests that the thrombin-occupied receptor is coupled to phospholipase activities by a pertussis toxin-insensitive guanine nucleotide regulatory protein in human endothelial cell membranes.
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PMID:Thrombin-induced prostacyclin biosynthesis in human endothelium: role of guanine nucleotide regulatory proteins in stimulus/coupling responses. 210 25

We have previously shown that vasopressin (VP) induces breakdown of membrane phosphoinositides in adrenal glomerulosa cells. In the present study we demonstrate that the accumulation of inositol phosphates (IP) measured in the presence of arginine vasopressin (AVP) is reduced if the cells are incubated in a calcium-free medium. This effect cannot be accounted for by modification of VP binding, reduction of inositol lipid labeling, or stimulation of inositol, 1,4,5,-triphosphate 5-monophosphatase. It mainly affects phospholipase-C activity, since this enzyme is highly sensitive to calcium. Ionomycine and nifedipine, which, respectively, increase and decrease the intracellular calcium concentration, also, respectively, stimulate and inhibit IP accumulation. In membranes prepared from pertussis toxin (IAP)-treated cells, AVP stimulates inositol monophosphate accumulation to the same extent as in membranes derived from untreated cells. However, in intact cells, IAP decreases the inositol monophosphate accumulation. This decrease probably involves calcium influx, since we show that AVP stimulates a unidirectional calcium influx, which is completely blocked by IAP treatment. In rat adrenal glomerulosa cells, the AVP-stimulated secretion of aldosterone is mainly under the control of calcium, since a full inhibition of its secretion is observed under conditions in which the calcium influxes are completely suppressed despite a sustained accumulation of IP (calcium depletion or IAP treatment). Together, these results signify that VP acts on rat glomerulosa cells by two distinct mechanisms: calcium influx, which is IAP sensitive, and phosphoinositide turnover, which is IAP insensitive.
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PMID:Involvement of distinct G-proteins in the action of vasopressin on rat glomerulosa cells. 210 33

We have previously demonstrated that influenza A virus (IAV) stimulates the human neutrophil through phospholipase C activation. With the use of the fluorescent indicator 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF), cytoplasmic acidification and subsequent alkalinization are shown to accompany this activation. These responses are not inhibited by pertussis toxin (PT). The alkalinization is mediated largely *but not entirely) by the Na(+)-H+ antiporter and is not initiated, or modulated, by the IAV-induced cytosolic Ca2+ (Cai2+) rise. Rather, protein kinase C (PKC) is likely the mediator of cell alkalinization, based on studies using the PKC inhibitor 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7). The acidification can be dissociated from the alkalinization response, which is also independent of Cai2+ fluxes and of PKC. Both pHi responses can be dissociated from the respiratory burst. Cytosolic alkalinization and acidification seem to reflect two independently mediated responses of the activated neutrophil, the former resulting ultimately from phospholipase activation and the latter from other activities that are not yet fully characterized.
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PMID:Human neutrophil stimulation by influenza virus: relationship of cytoplasmic pH changes to cell activation. 211 68

GnRH stimulates secretion of pituitary LH by increasing intracellular calcium. Increased calcium may result from activation of phospholipase-C, since there is an increase in inositol phosphates and diacylglycerol, and a redistribution of protein kinase-C (PKC) from cytosolic to a particulate cell fraction in GnRH-stimulated pituitary cultures. A GTP-binding protein (G-protein) may mediate GnRH actions, since GTP stimulates LH release in permeabilized gonadotropes and decreases receptor affinity for a GnRH analog. In the present study we have used sodium fluoride, an exogenous activator of G-proteins, to investigate the possibility of a G-protein link between GnRH receptor activation, phospholipase-C activity, and LH release. Treatment of primary pituitary cell cultures from immature female rats with sodium fluoride stimulated the release of 20% total cellular LH and increased inositol phosphate accumulation. Sodium fluoride-stimulated LH release was insensitive to cholera toxin and pertussis toxin. Sodium fluoride-stimulated LH release was additive with a maximally effective concentration of phorbol 12-myristate 13-acetate and was not inhibited by depletion of cellular PKC, suggesting that PKC does not mediate sodium fluoride effects. Treatment of cultures with 3 mM EGTA and 10 nM GnRH for 5 and 16 h reduced pituitary responsiveness to subsequent treatment with GnRH, but had no effect on sodium fluoride-stimulated LH release. Although the precise mechanism of sodium fluoride-stimulated LH release remains to be described, our results support a role for a G-protein in regulation of LH release by the releasing hormone.
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PMID:Stimulation of luteinizing hormone release by sodium fluoride is independent of protein kinase-C activity and unaffected by desensitization to gonadotropin-releasing hormone. 215 31

Polarized renal epithelial cells have pertussis toxin-sensitive Gi proteins at their apical membrane capable of modulating Na+ channel activity (Cantiello, H.F., Patenaude, C.R., and Ausiello, D.A. (1989) J. Biol. Chem. 264, 20867-20870). In this study, the patch clamp technique was used to assess if this Gi-mediated regulation of Na+ channels is a component of a phospholipid signal transduction pathway. In excised inside-out patches of apical membranes of A6 cells, guanosine 5'-(3-O-thio)triphosphate (GTP gamma S)-stimulated Na+ channel activity (percent open time and channel number) was inhibited by the phospholipase inhibitor mepacrine (50 microM), which had no effect on single channel conductance. In contrast, Na+ channel activity increased in a Ca2(+)-dependent manner following the addition of 100 nM mellitin to untreated or pertussis toxin-treated patches. Addition of 10 microM arachidonic acid in the presence of mepacrine increased Na+ channel activity. Both percent open time and Na+ channel number induced by GTP gamma S, the exogenous alpha i-3 subunit, or arachidonic acid were inhibited by the addition of the 5-lipoxygenase inhibitor nordihydroguaiaretic acid. Na+ channel activity was restored with the addition of leukotriene D4 (100 nM) or the parental leukotriene substrate 5-hydroperoxyeicosatetraenoic acid (10 microM). Thus, Gi activation of apical membrane epithelial Na+ channels is mediated through the regulation of phospholipase and lipoxygenase activities. This apically located signal transduction pathway may be sensitive to, or independent of, classical second messengers generated at the basolateral membrane and known to be responsible for modulation of Na+ channel activity in epithelia.
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PMID:G alpha i-3 regulates epithelial Na+ channels by activation of phospholipase A2 and lipoxygenase pathways. 217 82

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