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)

Leukotriene D4 (LTD4) at concentrations greater than 1 nM induced phosphatidylinositol bisphosphate (PIP2) hydrolysis and protein kinase C (PKC) activation in primary culture of airway smooth muscle cells. Within seconds of activation, an increase in inositol 1,4,5-trisphosphate (IP3) was observed reaching a maximum at 5 min. The level of IP3 decreased after 5 min and was followed by an increase in inositol 1,4-bisphosphate (IP2) and inositol 1-monophosphate (IP1). LTD4-induced PIP2 hydrolysis was inhibited by 1 h pretreatment of cells with 10 micrograms/ml of pertussis toxin (PTX). LTD4 activated both soluble and particulate forms of PKC by 2-3-fold. The LTD4-induced PKC activation was blocked by treatment of cells with PTX, suggesting the involvement of a PTX-sensitive G-protein. To assess the involvement of G(i) in smooth muscle cell receptor activation, the modulation of adenylyl cyclase activity was investigated. LTD4 did not stimulate cAMP formation in smooth muscle cells, and did not inhibit forskolin-induced cAMP formation. These data suggest that the LTD4 receptor in airway smooth muscle cells is coupled to a PTX-sensitive G-protein, possibly G(o).
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PMID:Polyphosphoinositide hydrolysis and protein kinase C activation in guinea pig tracheal smooth muscle cells in culture by leukotriene D4 involve a pertussis toxin sensitive G-protein. 133 Jun 44

A role for phospholipase C (PLC) hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) as a mechanism of alpha 1-adrenergic signal transduction in human airway epithelial cells (AEC) was investigated in isolated normal tracheal and cystic fibrosis (CF) nasal epithelial cells grown in in vitro culture and prelabeled with 3 muCi myo-[3H]inositol/ml for 72 h. Breakdown of polyphosphoinositides was measured using thin-layer chromatography to detect phosphatidylinositol, phosphatidylinositol 4-phosphate (PIP), and PIP2. Inositol phosphates were separated by ion-exchange column chromatography. In normal AEC, the addition of the endogenous catecholamine l-epinephrine produced a rapid, transient accumulation of inositol 1,4,5-trisphosphate (IP3) and inositol 1,4-bisphosphate (IP2) and breakdown of PIP and PIP2. IP3 increased 1.7-fold and IP2 1.6-fold after 20 and 40 s, respectively. A maximal decrease of 35% PIP2 and 30% PIP is observed after 20 and 40 s, respectively. The effects of l-epinephrine were not blocked by the beta-adrenergic antagonist dl-propranolol but were mimicked by the alpha 1-adrenergic agonist methoxamine. Prazosin, an alpha 1-adrenergic antagonist, and pertussis toxin (PTX) blocked the effects of l-epinephrine and methoxamine. Addition of l-epinephrine and methoxamine to CF nasal epithelial cells also induced prazosin-sensitive polyphosphoinositide breakdown and inositol phosphate accumulation. A 2.2-fold accumulation of IP3 was observed after 10 s and 2.0-fold increase in IP2 after 20 s. Maximal decreases of 32% PIP2 and 23% PIP levels were observed after 20-s incubation with l-epinephrine. PTX reduced the effects of l-epinephrine and significantly blocked the effects of methoxamine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alpha 1-adrenergic signaling in human airway epithelial cells involves inositol lipid and phosphate metabolism. 134

Platelet activating factor (PAF) was found to stimulate the metabolism of inositol phospholipids via deacylation and phospholipase C in Kupffer cells, the resident macrophages in liver. PAF-induced phosphoinositide metabolism occurred in two phases. Within seconds after stimulation, in the absence of extracellular Ca++, platelet activating factor caused the phosphodiester hydrolysis of phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 4-phosphate with the release of inositol 1,4,5-trisphosphate and inositol 1,4-bisphosphate. This was followed by an extracellular Ca(++)-dependent release of glycerophosphoinositol, inositol monophosphates and inositol bisphosphates. Various Ca(++)-mobilizing agonists failed to evoke hydrolysis of phosphoinositides. Platelet activating factor also stimulated the synthesis and release of prostaglandins from these cells. Platelet activating factor-stimulated phosphodiester metabolism of phosphoinositides and prostaglandin synthesis was inhibited by treatment with pertussis toxin and cholera toxin. Pertussis toxin also inhibited platelet activating factor-induced glycerophosphoinositol release. Cholera toxin, in contrast, stimulated platelet activating factor-induced glycerophosphoinositol release and prostaglandin synthesis and synergistically stimulated the effect of platelet activating factor on these processes. The results suggest that platelet activating factor-induced metabolism in the Kupffer cells occurs via specific receptors and may be mediated through the activation of different G-proteins.
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PMID:PAF effects on transmembrane signaling pathways in rat Kupffer cells. 166 3

Stimulation of rat Kupffer cells in primary culture with platelet-activating factor (PAF) caused a rapid hydrolysis of phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 4-phosphate with a concomitant increase in the levels of myo-inositol 1,4,5-trisphosphate and myo-inositol 1,4-bisphosphate. This phospholipase C-mediated hydrolysis of polyphosphoinositides was independent of extracellular Ca2+ but was inhibited by the intracellular Ca2+ antagonist TMB-8. A second slower response to PAF was characterized by deacylation of PI leading to the accumulation of glycerophosphoinositol (GPI). PAF-induced GPI synthesis was not inhibited by TMB-8. These effects of PAF were accompanied by initial transient mobilization of Ca2+ from intracellular stores followed by a rather slow influx of Ca2+ from the extracellular medium. PAF-stimulated deacylation and phosphodiesteric hydrolysis of inositol lipids were differentially affected by cholera toxin and pertussis toxin. Pretreatment of the Kupffer cells with either of these toxins caused inhibition of phospholipase C activity. Pertussis toxin also inhibited PAF-stimulated deacylation. However, cholera toxin itself stimulated GPI release and addition of PAF to the cholera toxin-treated cells caused a further increase in GPI release. Phorbol ester inhibited PAF-induced phosphodiesteric hydrolysis of phosphoinositides, but not deacylation. PAF-induced metabolism of phosphoinositides was inhibited by the PAF antagonist, U66985. These results suggest that PAF-induced phosphodiesteric hydrolysis and deacylation of inositol phospholipids are regulated via distinct mechanisms involving activation of separate G-proteins in rat Kupffer cells. Also the regulation of phosphoinositide metabolism by Ca2+ mobilization from two separate Ca2+ pools is indicated by this study.
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PMID:Two distinct pathways of platelet-activating factor-induced hydrolysis of phosphoinositides in primary cultures of rat Kupffer cells. 217 Apr 6

The m-cholinoceptor agonist carbachol elicits a negative inotropic effect in mammalian atria. Pretreatment with pertussis toxin converts the negative to a positive inotropic effect. In this study we investigated the time course of the effects of carbachol on force of contraction and phosphoinositide products in electrically driven left auricles from guinea pig hearts after pretreatment with pertussis toxin (180 micrograms/kg i.v.; 24 hr). Inositol phosphates and phosphatidylinositols were labeled with [3H]inositol and separated with high-performance liquid chromatography and thin-layer chromatography, respectively. All experiments were performed in the presence of LiCl (10 mmol/l). The positive inotropic effect of carbachol (10 mumol/l) began within 2 min and was maximal within 15 min. Inositol 1,4,5-trisphosphate rose within 1 min followed by an increase in inositol 1,3,4,5-tetrakisphosphate, inositol 1,3,4-trisphosphate, inositol 1,4-bisphosphate and inositol 1-phosphate beginning within 2 min. It is concluded that the carbachol-induced positive inotropic effect is associated with an increase in the presumed second messengers inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate. Since the increase in inositol 1,4,5-trisphosphate precedes the increase in force of contraction, it may initiate the positive inotropic effect. The increase in inositol 1,3,4,5-tetrakisphosphate may be involved in maintaining the positive inotropic effect of carbachol.
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PMID:Positive inotropic effect of carbachol and inositol phosphate levels in mammalian atria after pretreatment with pertussis toxin. 239 18

The plasma-membrane receptors, coupling mechanisms, and effector enzymes that mediate target-cell activation by angiotensin II (AII) have been characterized in rat and bovine adrenal glomerulosa cells. The AII holoreceptor is a glycoprotein of Mr approximately 125,000 under non-denaturing conditions. Photoaffinity labeling of AII receptors with azido-AII derivatives has shown size heterogeneity among the AII binding sites between species and target tissues, with Mr values of 55,000 to 79,000. Such variations in molecular size probably reflect differences in carbohydrate content of the individual receptor sites. The adrenal AII receptor, like that in other tissues, is coupled to the inhibitory guanine nucleotide inhibitory protein (Ni). However, studies with pertussis toxin have shown that stimulation of aldosterone production by AII is not mediated by Ni but by a pertussis-insensitive nucleotide regulatory protein of unidentified nature. Although Ni is not involved in the stimulatory action of AII on steroidogenesis, it does mediate the inhibitory effects of high concentrations of AII upon aldosterone production. The actions of AII on adrenal cortical function are thus regulated by at least two guanine nucleotide regulatory proteins that are selectively activated by increasing AII concentrations. The principal effector enzyme in AII action is phospholipase C, which is rapidly stimulated in rat and bovine glomerulosa after AII receptor activation. AII-induced breakdown of phosphatidylinositol bisphosphate (PIP2) and phosphatidylinositol phosphate (PIP) leads to formation of inositol 1,4,5-trisphosphate (IP3) and inositol 1,4-bisphosphate (IP2). These are metabolized predominantly to inositol-4-monophosphate, which serves as a marker of polyphosphoinositide breakdown, whereas inositol-1-phosphate is largely derived from phosphatidylinositol hydrolysis. The AII-stimulated glomerulosa cell also produces inositol 1,3,4-trisphosphate, a biologically inactive IP3 isomer formed from Ins-1,4,5-trisphosphate via inositol tetrakisphosphate (IP4) during ligand activation in several calcium-dependent target cells. The Ins-1,4,5-P3 formed during AII action binds with high affinity to specific intracellular receptors that have been characterized in the bovine adrenal gland and other AII target tissues, and may represent the sites through which IP3 causes calcium mobilization during the initiation of cellular responses.
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PMID:Angiotensin II receptors and mechanisms of action in adrenal glomerulosa cells. 282 11

Illumination induced an increase in inositol polyphosphates, inositol 1,4-bisphosphate and inositol 1,4,5-trisphosphate, in the photoreceptors of the squid, Loligo pealei. There was a concomitant decrease in phosphatidylinositol 4,5-bisphosphate, but no light-induced change in any other phosphoinositide. None of these stimulus-induced changes were altered by treatment in vivo with pertussis toxin, which ADP-ribosylated a Mr-39000-peptide. These findings support the hypothesis that inositol 1,4,5-trisphosphate participates as either a messenger or a modulator in transduction in invertebrate photoreceptors.
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PMID:Light-induced changes in the content of inositol phosphates in squid (Loligo pealei) retina. 282 25

Addition of gonadotropin releasing hormone (GnRH) to pituitary cells prelabeled with [32P]Pi or with myo-[2-3H]inositol, resulted in a rapid decrease in the level of [32P]phosphatidylinositol 4,5-bisphosphate (approximately 10 s), and in [32P]phosphatidylinositol 4-phosphate (approximately 1 min), followed by increased labeling of [32P]phosphatidylinositol and [32P]phosphatidic acid (1 min). GnRH stimulated the appearance of [3H]myo-inositol 1,4,5-trisphosphate (10 s), [3H]myo-inositol 1,4-bisphosphate (15 s), and [3H]myo-inositol 1-phosphate (1 min) in the presence of Li+ (10 mM). Li+ alone stimulated the accumulation of [3H]myo-inositol 1-phosphate and [3H]myo-inositol 1,4-bisphosphate but not [3H]myo-inositol 1,4,5-trisphosphate, but had no effect on luteinizing hormone release. The effect of GnRH on inositol phosphates (Ins-P) production was dose-related (ED50 = 1-5 nM), and was blocked by a potent antagonist [D-pGlu,pClPhe,D-Trp]GnRH. Elevation of cytosolic free Ca2+ levels ([Ca2+]i), by ionomycin and A23187 from intracellular or extracellular Ca2+ pools, respectively, had no significant effect on [3H]Ins-P production. GnRH-induced [3H]Ins-P production was not dependent on extracellular Ca2+ and was noticed also after extracellular or intracellular Ca2+ mobilization by A23187 or ionomycin, respectively. The effect of GnRH on [3H]Ins-P accumulation was not affected by prior treatment of the cells with the tumor promoter phorbol ester 12-O-tetradecanoylphorbol-13-acetate or with islet-activating protein pertussis toxin. These results indicate that GnRH stimulates a rapid phosphodiester hydrolysis of polyphosphoinositides. The stimulatory effect is not mediated via an islet-activating protein-substrate, is not dependent on elevation of [Ca2+]i, neither is it negatively regulated by 12-O-tetradecanoylphorbol-13-acetate which activates Ca2+/phospholipid-dependent protein C kinase. The results are consistent with the hypothesis that GnRH-induced phosphoinositide turnover is responsible for Ca2+ mobilization followed by gonadotropin release.
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PMID:Gonadotropin-releasing hormone activates a rapid Ca2+-independent phosphodiester hydrolysis of polyphosphoinositides in pituitary gonadotrophs. 301 78

Membranes prepared from DMSO-differentiated HL60 cells labeled with [3H]inositol hydrolyze polyphosphoinositides in a Ca2+-dependent manner, generating inositol 1,4-bisphosphate (IP2) and inositol 1,4,5-trisphosphate (IP3). Incubation of membranes with GTP or GTP gamma S reduces the concentration of Ca2+ required for activation. This nucleotide effect is potentiated by formyl-Met-Leu-Phe (FMLP). Pertussis toxin inhibits FMLP-induced augmentation, but not the induction of IP2/IP3 formation by GTP or GTP gamma S. These results suggest that differentiated HL60 cells contain a membrane-associated phospholipase C that degrades polyphosphoinositides and that activation of this enzyme is mediated by at least two guanine nucleotide binding proteins, one of which is linked to FMLP receptors and is pertussis toxin sensitive.
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PMID:Chemotactic peptide, calcium and guanine nucleotide regulation of phospholipase C activity in membranes from DMSO-differentiated HL60 cells. 303 41

1. The receptor-activated mechanisms that mediate the steroidogenic actions of angiotensin II (AII) have been characterized in rat and bovine adrenal glomerulosa cells. In rat adrenal cells, the AII receptor is coupled to a guanine nucleotide inhibitory protein which reduces adenylate cyclase activity and cyclic AMP production. However, receptor-mediated stimulation of aldosterone production by AII is exerted through a separate pertussis-insensitive nucleotide regulatory protein that subserves coupling of activated receptors to phospholipase C. 2. In AII-stimulated glomerulosa cells, hydrolysis of phosphatidylinositol (4,5)-bisphosphate (PIP2) by phospholipase C yields diacylglycerol and inositol 1,4,5-trisphosphate (Ins-P3), which act as second messengers by activating calcium-calmodulin and calcium-phospholipid dependent protein kinase pathways. Ins-1,4,5-P3 is a potent stimulus of intracellular calcium mobilization, and is promptly inactivated by two major routes of metabolism. Direct degradation of Ins-1,4,5-P3 by a 5-phosphatase gives inositol 1,4-bisphosphate which in turn is metabolized to inositol-4-monophosphate. The latter product can be derived only from higher inositol phosphates, and thus serves as a specific marker of polyphosphoinositide breakdown in agonist-stimulated cells. In contrast, inositol-1-phosphate is largely derived from phosphatidylinositol hydrolysis, which is not increased during the initial phase of AII action. 3. Ins-1,4,5-P3 formed in AII-stimulated glomerulosa cells is also phosphorylated by a calcium-calmodulin dependent 3-kinase to form inositol 1,3,4,5-tetrakisphosphate (Ins-P4), which is rapidly dephosphorylated to the biologically inactive Ins-1,4,5-P3 isomer, Ins-1,3,4-trisphosphate. The latter metabolite, like Ins-1,4,5-P3, is both degraded to lower phosphates (Ins-3,4,P2 and Ins-1,3-P2) and phosphorylated to form a new tetrakisphosphate isomer (Ins-1,3,4,6-P4). Ins-1,4,5-P3 formed during AII action is bound with high affinity to specific intracellular receptors through which InsP3 causes calcium mobilization during the initiation of cellular responses to AII and other calcium-dependent ligands.
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PMID:Control of glomerulosa cell function by angiotensin II: transduction by G-proteins and inositol polyphosphates. 315 62


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