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)

Prostaglandin F2 alpha (PGF2 alpha) stimulated the formation of inositol phosphates in a dose-dependent manner in cloned osteoblast-like MC3T3-E1 cells. This reaction was markedly inhibited dose-dependently by pertussis toxin. In the cell membranes, pertussis toxin-catalyzed ADP-ribosylation of a 40-kDa protein was significantly attenuated by pretreatment of PGF2 alpha. These results suggest that pertussis toxin-sensitive GTP-binding protein is involved in the coupling of PGF2 alpha receptor to phospholipase C in these cells.
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PMID:Involvement of pertussis toxin-sensitive GTP-binding protein in prostaglandin F2 alpha- induced phosphoinositide hydrolysis in osteoblast-like cells. 217 9

We previously reported that prostaglandin F2 alpha (PGF2 alpha) activates phosphatidylcholine-hydrolyzing phospholipase D independently from the activation of protein kinase C (PKC) in osteoblast-like MC3T3-E1 cells, and reported that pertussis toxin-sensitive GTP-binding protein (G-protein) is involved in the PGF2 alpha-induced phospholipase D activation. In this study, we examined the effect of retinoic acid (RA) on the phospholipase D activity stimulated by PGF2 alpha in these cells. The pretreatment of RA markedly inhibited the formation of choline induced by PGF2 alpha (10 microM) in a dose-dependent manner in the range between 1 nM and 0.1 microM. This inhibitory effect of RA was dependent on the time of pretreatment up to 8 h. However, RA had little effect on the choline formation induced by NaF, a G-protein activator, or 12-O-tetradecanoylphorbol-13-acetate, an activator of PKC. These results strongly suggest that RA suppresses the phospholipase D activated by PGF2 alpha in osteoblast-like cells and that the effect of RA is exerted at the point between PGF2 alpha receptor and G-protein.
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PMID:Effect of retinoic acid on prostaglandin F2 alpha-induced phospholipase D activity in osteoblast-like cells. 893 Nov 11

Pertussis toxin-insensitive GTP-binding protein was observed to be involved in prostaglandin F2 alpha (PGF2 alpha)-induced phosphoinositide metabolism in Chinese hamster ovary (CHO) cells transfected with PGF2 alpha receptor cDNA (CHO-PGF2 alpha R cells) (Ito, S. et al. Biochem. Biophys. Res. Commun. 200: 756,1994). In the present study, we investigated PGF2 alpha-induced PLD activation in CHO-PGF2 alpha R cells. PLD activation was examined by measuring the production of [3H]phosphatidylbutanol ([3H]PBut), a specific product of the PLD-catalyzed transphosphatidylation reaction. PGF2 alpha-induced [3H]PBut formation was concentration-dependent with the maximal level obtained at 1 microM PGF2 alpha. The maximal [3H]PBut formation was observed at 2 min after addition of PGF2 alpha. Depletion of extracellular Ca2+ with EGTA suppressed PGF2 alpha-induced PLD activation by 50%. PKC inhibitors Ro31-8425 and calphostin C inhibited PGF2 alpha-induced [3H]PBut formation by 50%. PTK inhibitors genistein and herbimycin A failed to inhibit PGF2 alpha-induced PLD activation. A combination of maximal effective concentrations of PGF2 alpha (1 microM) and PMA (100 nM) enhanced PLD activation in an additive manner. Pretreatment of the cells with PMA for 2 h down-regulated PKC alpha and decreased PGF2 alpha-induced PLD activation. These results suggest that PLD activation by PGF2 alpha is mediated by both PKC-dependent and -independent pathways and that PKC alpha is involved in the former pathway.
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PMID:PLD activation in Chinese hamster ovary (CHO) cells transfected with PGF2 alpha receptor cDNA. 893 84

The objective of this study was to investigate the mechanism of action of PGF2 alpha in cultured human myometrial cells. We measured the effects of PGF2 alpha and fluprostenol, a selective PGF2 alpha receptor (FP receptor) agonist, on phospholipase C(PLC) activation, on changes in the intracellular free calcium concentration ([Ca2+]i), and on protein tyrosine phosphorylation. PGF2 alpha and fluprostenol activated PLC (determined by measuring the formation of inositol phosphates) and increased [Ca2+]i in a concentration-dependent manner. The apparent affinity of the FP receptor for fluprostenol was higher than that for PGF2 alpha when measuring PLC activation, but the receptor displayed similar affinities for both agonists when measuring increases in [Ca2+]i. These effects were not altered by treating the cells with pertussis toxin (PT), suggesting that the FP receptor is linked to PLC activation by a G protein of the Gq family. By contrast, the effect of oxytocin on PLC activation involved both PT-resistant and PT-sensitive pathways. Human myometrial cells responded to pervanadate and epidermal growth factor with increased PLC activity and increased tyrosine phosphorylation, demonstrating a functional PLC-gamma tyrosine kinase pathway. However, neither fluprostenol nor oxytocin stimulated tyrosine phosphorylation, but the effects of both agonists were inhibited after protein kinase C stimulation. These data suggest that fluprostenol and oxytocin activate PLC-beta rather than PLC-gamma isoforms. The effect of fluprostenol is Ca2+ dependent, but is unlikely to involve a direct effect of Ca2+ on PLC activity.
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PMID:Fluprostenol activates phospholipase C and Ca2+ mobilization in human myometrial cells. 896 35

Prostaglandin F2 alpha (PGF2 alpha) has regulatory (mainly luteolytic) effects in the ovary but the mechanism of action is not completely understood. Reverse transcriptase-polymerase chain reaction (RT-PCR) techniques were used to demonstrate the presence of mRNA encoding the PGF2 alpha receptor (FP receptor) in human granulosa-lutein cells. Specific primers for the amplification of cDNA were designed and yielded a single product of 696 bp corresponding to the FP receptor. The identity of this product was verified by sequencing. Fluprostenol, a selective FP receptor agonist, activated phospholipase C (PLC) and increased intracellular free calcium concentration, confirming the functional activation of the receptor. We have demonstrated by Western blotting that granulosa cells express PLC-beta and PLC-gamma isoforms. The cells responded to pervanadate with increased PLC activity and increased tyrosine phosphorylation, demonstrating a functional PLC-gamma tyrosine kinase pathway. However, fluprostenol did not provoke any detectable tyrosine phosphorylation. Moreover, the effect of fluprostenol was inhibited through protein kinase C stimulation by phorbol 12, 13-dibutyrate, and was not affected when cells were treated with phenylarsine oxide, which blocks tyrosine phosphorylation. These results suggest that the FP receptor activates PLC-beta rather than PLC-gamma isoforms. Fluprostenol-induced activation was pertussis toxin resistant. Granulosa cells express G proteins of the Gq family (resistant to pertussis toxin) and mRNA for both G alpha q and G alpha 1 l has been identified by RT-PCR. In conclusion, human granulosa cells have a functional FP receptor the effects of which are mediated through PLC-beta activation probably via Gq/1 l.
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PMID:Activation of the prostaglandin FP receptor in human granulosa cells. 946