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

Human parathyroid adenomas are aberrantly regulated by extracellular calcium. We tested pertussis toxin, which ADP-ribosylates and inactivates several guanine nucleotide regulatory proteins, to test the role of these proteins in the secretory control of adenomatous parathyroid tissue. Pertussis toxin did not affect basal cAMP accumulation in 12 adenomas and enhanced parathyroid hormone (PTH) release in 6 of 10 adenomas. Prostaglandin F2 alpha (PGF2 alpha) inhibited cAMP in three of six adenomas, and pertussis toxin pretreatment did not affect this result. PTH release in 7 of 10 adenomas was inhibited by PGF2 alpha, and pertussis toxin did not significantly alter PTH release. Pertussis toxin catalyzed ADP-ribosylation of a 40-kDa protein in all adenomas tested (n = 8). We conclude that cAMP accumulation was not affected by pertussis toxin but that in 6 of 10 adenomas, the toxin enhanced PTH release. We suggest that cAMP accumulation and PTH release may be uncoupled from negative control by inhibitory ligands in adenomatous tissue or that the G-proteins involved do not couple to regulatory receptors or to effector.
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PMID:Effect of prostaglandin F2 alpha on human parathyroid adenomas: evidence for uncoupling of parathyroid hormone secretion and cAMP accumulation. 285 Jul 25

Prostaglandin F2 alpha (PGF2 alpha) and alpha-adrenergic agonists inhibit cAMP production and PTH secretion in dispersed bovine parathyroid cells. We have tested the mechanism of these effects utilizing pertussis toxin which catalyzes ADP ribosylation and inactivation of the inhibitory adenylate cyclase coupling protein Ni. Dispersed bovine parathyroid cells treated with or without 0.5 micrograms/ml pertussis toxin were tested with stimulatory (epinephrine, isoproterenol) or inhibitory (PGF2 alpha) agonists for responses in cAMP accumulation (5-min incubation) or PTH (90-min incubation) release. Pertussis toxin produced an enhanced response to epinephrine (a mixed alpha-adrenergic and beta-adrenergic agonist) in cAMP production and in PTH secretion. PGF2 alpha inhibited intracellular cAMP by 40% and PTH secretion by 35%. Pertussis toxin treatment of bovine parathyroid cells reduced the PGF2 alpha inhibition. We conclude that: 1) inhibition of PTH release by PGF2 alpha and alpha-adrenergic agonists parallels inhibition of cAMP production; 2) pertussis toxin blocks the inhibitory actions of PGF2 alpha and alpha-adrenergic agents on cAMP accumulation and PTH secretion; 3) the inhibitory coupling protein Ni mediates the inhibitory effects of these agents.
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PMID:Prostaglandin F2 alpha and alpha-adrenergic agonists regulate parathyroid cell function via the inhibitory guanine nucleotide regulatory protein. 287 Sep 12

15-Hydroxyeicosatetraenoic acid [15-(S)-HETE], a major arachidonic acid metabolite produced from the 15-lipoxygenase pathway, has been characterized as an antiinflammatory cellular mediator since it can inhibit the in vivo and in vitro formation of the proinflammatory leukotrienes via the 5-lipoxygenase pathway in various cells. 15-HETE has been confirmed to inhibit the 5-lipoxygenase in rat basophilic leukemia cell (RBL-1) homogenates with an I50 = 7.7 microM. The I50 of the 12-HETE isomer was 6 microM whereas prostaglandin F2 alpha was ineffective. In order to examine the mechanistic basis underlying the inhibitory action of 15-HETE, association assays of [3H]-15-HETE with RBL-1 subcellular fractions were carried out. The presence of the zwitterionic detergent CHAPS enhanced specific [3H]-15-HETE binding in the membrane fractions three-fold and specific 15-HETE binding was distributed among the nuclear (32%)-, granule (19%)-, plasma membrane (35%)-, and cytosol (14%)-enriched fractions. Studies using combined granule and plasma membrane enriched-, CHAPS treated-fractions showed that [3H]-15-HETE binding was time-dependent, specific and reversible, sensitive to pertussis toxin treatment, and indicated a single class of binding sites with a Kd = 460 +/- 160 nM and Bmax = 5.0 +/- 1.1 nM. Competition experiments showed that the order of 15-HETE or analogs in inhibiting the binding of [3H]-15-HETE was: 15(S)-HETE > or = 12-(S)-HETE = 5-(S)-HETE > 15-(R)-HETE > arachidonic acid. Prostaglandin F2 alpha and lipoxin B4 were ineffective as competitors. The similar profiles of the binding assays and inhibition of the 5-lipoxygenase suggest that 15-HETE binding sites may mediate this inhibitory action of 15-HETE.
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PMID:Characterization of specific subcellular 15-hydroxyeicosatetraenoic acid (15-HETE) binding sites on rat basophilic leukemia cells. 778 91

Of the various arachidonate cyclooxygenation eicosanoids synthesized in the normal and injured renal glomerular capillary, prostaglandin F2alpha (PGF2alpha) is the most abundant and potent in eliciting signaling events and biologic responses including contraction and proliferation of glomerular capillary pericytes known as mesangial cells. The regulation of PGF2alpha-induced signaling in these cells is unknown. The present studies assessed two key signaling events in response to PGF2alpha in mesangial cells; activation of phospholipase C (PLC) and protein kinase C (PKC). Mechanisms regulating PLC activation were also explored. Incubation of cultured growth arrested rat mesangial cells with PGF2alpha (1 microM) resulted in activation of a phosphatidyl inositol-specific phospholipase C (PI-PLC) assessed as increased generation of polyphosphates in myo-[3H]-inositol-labeled cells and as increased diacylglycerol (DAG) mass levels measured by a radioenzymatic assay. Generation of both inositol 1,4,5-trisphosphate and inositol 1,3,4-trisphosphate occurred, the former constituting 70% of total inositol trisphosphates. Enhanced generation of inositol 1,4-bisphosphate (IP2) also occurred and was greater than that of inositol 1,4,5-trisphosphate (IP3), indicating that PI-PLC utilized the phosphatidyl inositol monophosphate (PIP) to a greater extent than the phosphatidyl inositol bisphosphate (PIP2) substrate. Generation of DAG in response to PGF2alpha occurred in a biphasic pattern characterized by an early transient rise that peaked concomitantly with IP3 at 15 sec, and a late sustained increase at 2, 5, and 15 min that was not associated with an increase in IP3. PGF2alpha also activated PKC assessed as translocation of enzyme activity from cytosolic to membrane fractions. Inhibition of PKC using H-7 enhanced PGF2alpha-induced generation of IP3 at 15 sec but attenuated generation of DAG at 15 min. A more selective PKC inhibitor, Calphostin C, dose-dependently increased basal IP3 generation and also attenuated generation of DAG in response to PGF2alpha. This indicates that PKC negatively modulates PGF2alpha-induced PI-PLC activation, and that the late sustained DAG generation in response to PGF2alpha is regulated by a PKC-dependent phospholipase other than PLC. The mechanisms of PI-PLC stimulation in response to PGF2alpha were further explored using inhibitors of protein tyrosine phosphorylation and of guanine nucleotide-binding (G) protein activation. Inhibition of protein tyrosine phosphorylation using genistein had no effect on IP3 or DAG generation. ADP ribosylation of Gi using pertussis toxin (PTx) had no effect on IP3 generation in response to PGF2alpha. The inhibitor of receptor-coupled PI-PLC activation aminosteroid compound U-73122 that blocks G(PLC) was also ineffective. The observations indicate that PGF2alpha stimulates a PI-PLC which is under negative feedback regulatory control by PKC, and a phospholipase other than PLC which is under positive regulatory control by PKC. PGF2alpha-induced PI-PLC activation is independent of protein tyrosine phosphorylation and of PTx-sensitive G proteins.
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PMID:PGF2alpha-induced signaling events in glomerular mesangial cells. 865 Feb 55

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

Through selective activation of the gonadotropic signal transduction pathway, we have determined the probable site of the antigonadotropic effects of prostaglandin F2alpha (PGF2alpha) in the human granulosa-luteal cell (hGLC). The gonadotropic signal transduction pathway was activated at the level of the receptor (luteinizing hormone and beta-adrenergic), stimulatory G protein (Gs), adenylate cyclase (AC), and protein kinase A (PKA) by human chorionic gonadotropin (hCG) and isoproterenol (Iso), cholera toxin (CTX), forskolin, and dibutryl cAMP (Db cAMP), respectively. Concomitantly, the ability of PGF2alpha to inhibit progesterone production in response to the activation of this cascade at these different levels was examined. hGLCs were obtained from in vitro fertilization patients and were precultured for 8 d in Medium 199 supplemented with fetal bovine serum (M199; 10% FBS). Following the preculture period, cells were treated with either vehicle or one of the above activators of the gonadotropic pathway, either in the absence or presence of PGF2alpha (in M199; No FBS). Following the treatment period, media were collected and assayed for progesterone by RIA. Prostaglandin F2alpha (10(-6) M) significantly inhibited hCG (1 IU/mL), Iso (10(-5) M), CTX (1 microg/mL), and forskolin- (10(-5) M) stimulated progesterone production. Conversely, PGF2alpha did not inhibit progesterone production stimulated by a saturating concentration of Db cAMP (10(-6) M). The ability of PGF2alpha to inhibit hCG- or CTX-stimulated progesterone production was attenuated by pertussis toxin (PTX; 50 ng/mL). In conclusion, through a pertussis toxin-sensitive G protein, PGF2alpha inhibits progesterone production at a level below AC, and above the activation of PKA by cAMP.
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PMID:Stepwise activation of the gonadotropic signal transduction pathway, and the ability of prostaglandin F2alpha to inhibit this activated pathway. 974 35

We measured the effects of stable thromboxane A2 (TXA2) analogues on signalling in cultured human myometrial cells. U46619 and/or IBOP stimulated total inositol phosphates (IPs) and cAMP production, RhoA-associated protein kinase (ROK) activity and elevated intracellular calcium [Ca2+]i. Pretreatment of the cells with pertussis toxin did not inhibit IPs or [Ca2+]i production but the thromboxane receptor (TP) antagonist SQ-29548 did inhibit IPs and cAMP production, the elevation of [Ca2+]i, and the increase in ROK activity. Pretreatment with thapsigargin inhibited [Ca2+]i elevation. TP receptor-stimulated ROK activity was inhibited by the ROK inhibitor Y27632 while ROK activity was enhanced by the caspase 3 inhibitor, Z-DEVD-FMK. TP receptor-stimulated IPs production is additive to prostaglandin F2alpha (FP) or prostaglandin E (EP) receptor-stimulated IPs production and neither FP nor EP receptor-stimulated IPs production is inhibited by SQ29548. Thus cultured human myometrial cells express at least two functional TP receptor subtypes; TPalpha-like (cAMP-stimulating) and TPbeta-like (IPs, [Ca2+] and ROK-stimulating).
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PMID:Thromboxane receptor signalling in human myometrial cells. 1178 96