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 administration of 0.1-0.5% of ethanol produces a slow increase in the transepithelial potential (TEP) of about 2 mV in the bovine pigment epithelium (RPE) under ordinary room lighting. However, virtually no response could be observed when ethanol was administered in the dark. Because of this apparent light sensitivity, the ethanol induced response (EIR) was investigated to determine its spectral response characteristics, temporal interaction with light, and the effects of a variety of metabolic inhibitors as well as pertussis and cholera toxins. The spectral response curve peaked at 520 nm with a narrow half width. The EIR was found to be inhibited by pertussis toxin but not cholera toxin. Inhibition of either phospholipase A2 or lipoxygenase/cyclooxygenase resulted in a marked inhibition of the EIR. The incubating solutions of the apical surface of bovine and cultured chick embryo RPE were analyzed by RP-HPLC under conditions of weak white light and darkness. Two peaks in the chromatogram were observed to vary with these conditions and the presence of nordihydroguaiaretic acid simulated the effects of darkness. The RP-HPLC studies did not involve the employment of ethanol. Two different experimental procedures revealed the photosensitivity of the isolated RPE to weak light and suggest that light initiates or promotes arachidonic acid metabolism. A possible regulatory effect of retinoids was also indicated.
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PMID:Photosensitivity of the isolated pigment epithelium and arachidonic acid metabolism: preliminary results. 780

We previously reported that prostaglandin F2 alpha (PGF2 alpha) stimulates phosphoinositide hydrolysis via pertussis toxin-sensitive GTP-binding protein in osteoblast-like MC3T3-E1 cells (Miwa, Tokuda, Tsushita, Kotoyori, Takahashi, Ozaki, Kozawa and Oiso 1990) and that PGF2 alpha stimulates arachidonic acid release and prostaglandin E2 (PGE2) synthesis, and the activation of protein kinase C (PKC) amplifies the effect of PGF2 alpha in MC3T3-E1 cells (Tokuda, Oiso and Kozawa 1992). In the present study, we investigated the effect of retinoic acid (RA), a vitamin A (retinol) metabolite, on PGF2 alpha-induced PGE2 synthesis in MC3T3-E1 cells. The pretreatment with RA, which by itself had little effect on synthesis, significantly inhibited PGE2 synthesis induced by PGF2 alpha in a dose-dependent manner in the range between 1 nM and 0.1 microM. This effect of RA was dependent on the time of pretreatment up to 8 h. In addition, RA inhibited the amplification of PGF2 alpha-induced PGE2 synthesis by 12-O-tetradecanoylphorbol-13-acetate, known to be a PKC activator. However, RA had little effect on PGE2 synthesis induced by melittin, known as a phospholipase A2 activator. Moreover, pertussis toxin had little effect on arachidonic acid release induced by PGF2 alpha. These results strongly suggest that RA inhibits PGE2 synthesis induced by PGF2 alpha in osteoblast-like cells and the inhibitory effect is exerted at the point prior to the activation of phospholipase A2.
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PMID:Effect of retinoic acid on prostaglandin F2 alpha-induced prostaglandin E2 synthesis in osteoblast-like cells. 780 33

The regulation of phospholipase A2 by G protein-coupled receptors is examined in CHO cells which normally express the purinergic receptor and have been transfected with bovine rhodopsin. The purinergic receptor has been reported to activate both phospholipase C and phospholipase A2 in this cell line. In contrast, bovine rhodopsin by itself is not able to activate phospholipase A2. However, the photoreceptor does potentiate purinergic receptor-mediated phospholipase A2 activation in a light-dependent manner. Both the purinergic receptor stimulation of phospholipase A2 and the enhanced activity mediated by rhodopsin are completely pertussis toxin-sensitive, suggesting the regulation of phospholipase A2 by a member of the Gi family of G proteins. Both of these receptors also inhibit adenylyl cyclase activity. Rhodopsin-mediated inhibition of adenylyl cyclase is pertussis toxin-sensitive, whereas inhibition by the purinergic receptor is calcium-sensitive but not pertussis toxin-sensitive. These results suggest (1) that rhodopsin is similar to other receptors that normally couple to Gi when expressed in cultured cells and (2) that regulation of adenylyl cyclase and PLA2 in CHO cells by rhodopsin and the purinergic receptor occur via distinct pathways.
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PMID:The coupling of pertussis toxin-sensitive G proteins to phospholipase A2 and adenylyl cyclase in CHO cells expressing bovine rhodopsin. 781 32

Organic lead and tin compounds stimulate an increase of free arachidonic acid (AA) in HL-60 cells. This fatty acid is involved in numerous health problems and physiological mechanisms. Three major pathways result in a liberation of AA from membrane phospholipids and there is evidence that G-proteins serve as couplers within all three pathways. Therefore we investigated the influence of pertussis toxin (PT) on the organometallic-induced AA liberation. The effect of all studied compounds (organotin and organo-lead) was diminished by PT. We conclude that the organometals activate PLA2 to some extent via a PT-sensitive pathway. The ionophor A 23187 (1-10 microM) led to an increase of free AA by raising the intracellular Ca2+ level. One of the postulated ways of AA release is via Ca2+ channel activation; phospholipases are Ca2+ dependent. Thus, we examined the necessity of free intracellular Ca2+ for the organometallic effect. The Ca2+ chelator EGTA inhibited the increase of free AA induced by organometals. This is true also for verapamil, a Ca2+ channel blocker. Quinacrine, which is thought to be an inhibitor of phospholipase A2 (PLA2), prevented the AA liberation from membrane phospholipids induced by organometals. This could be due to the inhibition of PLA2, but it could also be the result of an inhibited Ca2+ influx.
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PMID:Effects of organometals on cellular signaling. I. Influence of metabolic inhibitors on metal-induced arachidonic acid liberation. 784 28

Endothelins are potent peptide mediators that elicit glycogenolytic and vasoconstrictor actions in the liver. Endothelins were found to stimulate the synthesis and release of the lipid mediator platelet-activating factor in cultured rat Kupffer cells. Endothelin-mediated synthesis of platelet-activating factor required extracellular calcium in that the calcium chelator, EGTA and nifedipine, a calcium ion channel blocker, inhibited platelet-activating factor synthesis. The phospholipase A2 inhibitor, 4-bromophenacyl bromide, strongly inhibited endothelin-induced platelet activating factor synthesis. Endothelin-stimulated platelet activating factor synthesis was inhibited after treatment of Kupffer cells with cholera toxin, whereas pertussis toxin inhibited only this response to endothelin-1. Agents that elevate intracellular cyclic AMP levels were found to inhibit endothelin-induced platelet-activating factor synthesis in Kupffer cells. Staurosporine, a protein kinase C inhibitor minimized endothelin-induced platelet-activating factor synthesis but phorbol myristate acetate, an activator of protein kinase C, did not affect endothelin-induced platelet activating factor synthesis. Thus, the current study demonstrates that activation of an endothelin receptor in cultured rat Kupffer cells results in the synthesis and release of platelet-activating factor. The importance of endothelin-mediated platelet-activating factor synthesis relates to the mechanism of intercellular signaling occurring between endothelial cells (i.e., the site of endothelin synthesis) and Kupffer cells (i.e., the site of formation of secondary mediators such as platelet-activating factor and eicosanoids) within the rat liver exposed to various types of pathophysiological episodes.
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PMID:Endothelin stimulates platelet-activating factor synthesis by cultured rat Kupffer cells. 784 29

Cellular responses to changes in the extracellular environment are mediated by intracellular signaling systems. One of the most extensively studied systems is adenylate cyclase which generates the second messenger molecule cAMP. Another one is the phosphatidylinositol (PI) second messenger system giving rise to IP3 and diacylglycerol, the latter stimulating protein kinase C. Recently, a third potential signaling system has attracted increased scientific attention: the phospholipase A2 system which generates arachidonic acid. This substance may be used for eicosanoid synthesis or serve as a second messenger molecule. The present report gives more evidence about mechanisms how these signaling pathways interact in cultured astrocytes. Substances commonly used for stimulation of arachidonic acid release and prostaglandin synthesis in these cultures (A23187, TPA) had no influence on intracellular cAMP levels. Pertussis toxin that had previously been shown to inhibit prostaglandin synthesis, had no influence on cAMP levels either. Cholera toxin, however, raised intracellular cAMP significantly, although much less than the beta-adrenoceptor agonist isoproterenol. Cholera toxin also caused a marked change in astroglial morphology even at reduced concentrations (1-10 ng/ml). A23187 used in combination with Ctx had a moderate stimulatory effect on cAMP synthesis. In contrast, in the presence of Ctx, the PKC-activating phorbol ester TPA synergistically stimulated cAMP production, raising cAMP levels as high as isoproterenol-stimulated levels. The TPA effect was concentration-dependent. It was also dependent on an intact PKC since preincubation of cells with the phorbol ester completely abolished the synergistic effect. The synergistic effect of the phorbol ester was also observed at subthreshold concentrations of isoproterenol. The data reveal that the sole activation of most Gs molecules is a necessary but not sufficient prerequisite to achieve maximal adenylate cyclase activity. The fine-tuning of this activity apparently occurs at the catalytic subunit which is under the (partial) control of phosphorylation by PKC.
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PMID:The phorbol ester TPA potentiates cholera toxin- and isoproterenol-stimulated cyclic AMP-synthesis in primary astrocyte cultures. 790 11

As shown on cultured astrocytes from the mouse, in the presence of adenosine deaminase, 2-chloroadenosine by acting on A1-adenosine receptors potentiated the activation of phospholipase C induced by the alpha 1-adrenergic agonist, methoxamine. This potentiation required the presence of external calcium and was blocked by pertussis toxin. Moreover, this potentiation resulted from a cascade of events: activation (by calcium and protein kinase C) of a phospholipase A2 coupled to A1-adenosine receptors, release of arachidonic acid, which inhibited the reuptake of glutamate into astrocytes and finally additional activation of phospholipase C by externally accumulated glutamate through metabotropic receptors. The effects of 2-chloroadenosine and methoxamine were respectively mimicked by somatostatin and substance P while endothelins reproduced the combined effects of 2-chloroadenosine and methoxamine. Conditioned media from treated astrocytes enriched in glutamate stimulated phospholipase C in cultured striatal neurones. In addition, glutamate alone was also found to stimulate phospholipase A2 in astrocytes through receptors exhibiting a pharmacological profile distinct from metabotropic receptors coupled to phospholipase C and the glutamate response was potentiated by ATP. Moreover, the neuronal arachidonic acid production evoked by glutamate was potentiated by acetylcholine. Finally, the combined application of 2-chloroadenosine and methoxamine on striatal astrocytes reduced the permeability of gap junctions between astrocytes and this response was mimicked by arachidonic acid. Together, these results emphasized the contribution of astrocytes in the regulation of glutamatergic transmission.
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PMID:Glial receptors and their intervention in astrocyto-astrocytic and astrocyto-neuronal interactions. 792 48

Previous studies have shown that a single type of transmembrane receptor is able to regulate multiple effectors through the activation of heterotrimeric G proteins. For example, the m2 muscarinic acetylcholine receptor (mAChR) expressed in Chinese hamster ovary (CHO) cells inhibits adenylyl cyclase, stimulates phospholipase C-dependent intracellular Ca2+ release, and activates phospholipase A2 through pertussis toxin-sensitive G proteins. However, it is unclear whether multiple effector enzymes can be regulated by one type of heterotrimeric G protein within a single cell. To investigate this question, we constructed a derivative of G alpha i3 (termed G alpha i3 C > S) in which the carboxyl-terminal cysteine residue, the site for pertussis toxin modification, was changed to a serine. Following pertussis toxin treatment of transfected CHO cells expressing the m2 mAChR, we found that the G alpha i3 C > S protein underwent guanine nucleotide exchange in response to the muscarinic agonist carbachol, while the m2 mAChR failed to activate the endogenous G alpha i2 and G alpha i3 proteins. Moreover, coupling of heterotrimeric G proteins containing G alpha i3 C > S to the m2 mAChR resulted in pertussis toxin-resistant inhibition of adenylyl cyclase, stimulation of phospholipase C-induced intracellular Ca2+ release, and phospholipase A2-mediated arachidonic acid release. Therefore, these studies provide conclusive evidence that heterotrimeric G proteins containing just G alpha i3 can regulate multiple effector enzymes within the same cell type.
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PMID:Heterotrimeric G proteins containing G alpha i3 regulate multiple effector enzymes in the same cell. Activation of phospholipases C and A2 and inhibition of adenylyl cyclase. 796 42

The pharmacological profile of coupling of the cloned human serotonin [5-hydroxytryptamine] (5-HT)1E receptors to second messengers was studied in African green monkey kidney cells (BS-C-1). At low concentrations (0.1-100 nM), 5-HT inhibited forskolin-stimulated cAMP accumulation (FSCA) by up to 90% whereas at higher concentrations it potentiated FSCA; potentiation was dependent on receptor density. Pretreatment of cells with pertussis toxin (PTx) or cholera toxin (CTx) eliminated agonist-induced inhibition and potentiation of FSCA, respectively. The potentiation of FSCA was not due to activation of phospholipase C and/or phospholipase A2 since 5-HT had no effect on inositol phosphate release, intracellular Ca2+ mobilization or arachidonic acid mobilization; neither was it affected by pretreatment with the nonselective phospholipase A2 inhibitor, quinacrine, or by the removal of extracellular Ca2+. The pharmacological profiles of the 5-HT1E receptor-mediated inhibition and potentiation of FSCA were very similar, although agonists displayed higher affinity for the former. These results indicate that the human 5-HT1E receptors can potentially couple, with similar pharmacological profiles, to multiple effector pathways. However, the potency and intrinsic activity of the compounds eliciting these responses can differ significantly, depending on the receptor density and the effector pathway studied.
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PMID:The cloned human 5-HT1E receptor couples to inhibition and activation of adenylyl cyclase via two distinct pathways in transfected BS-C-1 cells. 798 78

Cell-free synovial fluid from patients with rheumatoid arthritis contains soluble and insoluble IgG-containing immune complexes which activate reactive oxidant production in human neutrophils. In this report we have measured the effects of inhibitors of signal transduction pathways on neutrophil activation by these complexes and also following activation by synthetic soluble and insoluble immune complexes made from human serum albumin (HSA) and anti-(HSA) antibodies. In all aspects studied, the soluble rheumatoid complexes and the soluble synthetic complexes were indistinguishable in the ways in which they activated neutrophils. Activation of reactive oxidant production in response to these soluble complexes was completely inhibited by pertussis toxin (indicating G-protein coupling of receptor occupancy), completely insensitive to staurosporine (indicating that oxidant production did not require protein kinase C activity), only marginally (< 30%) inhibited by butanol (indicating that dependence upon activity of phospholipase D was minimal), and completely inhibited by chloracysine, an inhibitor of phospholipase A2. In contrast, activation of reactive oxidant production in response to the insoluble rheumatoid or insoluble synthetic immune complexes was largely pertussis toxin insensitive, inhibited by > 50% by staurosporine, inhibited by > 50% by butanol, and completely inhibited by chloracysine. These results show that the receptor-mediated signal transduction systems activated by the soluble and insoluble immune complexes are different. Because the soluble complexes activate a transient burst of reactive oxidant secretion from primed neutrophils, the mechanisms regulating either the release or the intracellular production of oxidants within rheumatoid joints are distinct and hence may be pharmacologically modified independently of each other.
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PMID:Stimulation of reactive oxidant production in neutrophils by soluble and insoluble immune complexes occurs via different receptors/signal transduction systems. 800 62


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