UMLS:C0043167 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

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

Prostaglandin E2 (PGE2) specifically bound to 100,000 X g pellet prepared from bovine adrenal medulla, and [3H]PGE2-bound proteins were solubilized with 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid. The dissociation of bound [3H]PGE2 from the proteins was enhanced by GTP. [3H]PGE2-specifically bound proteins were adsorbed onto a wheat germ agglutinin column and GTP treatment decreased the amount of [3H]PGE2 retained on the column. When [3H]PGE2-bound proteins were cross-linked in the membrane by dithiobis(succinimidyl propionate) and solubilized, bound [3H]PGE2 was no longer dissociated by GTP treatment, suggesting that cross-linking produced a stable and high-affinity complex of PGE receptor with a GTP-binding protein. Covalent cross-linking of the complex was attested by adsorption of dithiobis(succinimidyl propionate)-treated [3H]PGE2-bound proteins to GTP-Sepharose, and co-elution of [35S]guanosine 5'-O-(3-thiotriphosphate) binding activity and immunoreactivities of alpha o and beta subunits of a GTP-binding protein. The cross-linked [3H]PGE2-bound complex was eluted as an apparently single radioactive peak at the position of Mr = 200,000 by gel filtration. These results have demonstrated that PGE receptor is a glycoprotein with an approximate Mr of 110,000, assuming that the Mr of the GTP-binding protein is 90,000. PGE2 neither activated nor inhibited adenylate cyclase activity, and pertussis toxin (islet-activating protein) did not affect PGE2 binding and its GTP sensitivity. These results suggest that the PGE receptor may be functionally associated with a pertussis toxin-insensitive GTP-binding protein and is not coupled to the adenylate cyclase system in bovine adrenal medulla.
...
PMID:Covalent cross-linking of prostaglandin E receptor from bovine adrenal medulla with a pertussis toxin-insensitive guanine nucleotide-binding protein. 288 64

Prostaglandin E2 (PGE2) was found to bind specifically to a 100,000 x g pellet prepared from bovine adrenal medulla. The PGE receptor was associated with a GTP-binding protein (G-protein) and could be covalently cross-linked with this G-protein by dithiobis(succinimidyl propionate) in the 100,000 x g pellet (Negishi, M., Ito, S., Tanaka, T., Yokohama, H., Hayashi, H., Katada, T., Ui, M., and Hayaishi, O. (1987) J. Biol. Chem. 262, 12077-12084). In order to characterize the G-protein associated with the PGE receptor and reconstitute these proteins in phospholipid vesicles, we purified the G-protein to apparent homogeneity from the 100,000 x g pellet. The G-protein served as a substrate of pertussis toxin but differed in its alpha subunit from two known pertussis toxin substrate G-proteins (Gi and Go) purified from bovine brain. The molecular weight of the alpha subunit was 40,000, which is between those of Gi and Go. The purified protein was also distinguished immunologically from Gi and Go and was referred to as Gam. PGE receptor was solubilized by 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid and freed from G-proteins by wheat germ agglutinin column chromatography. Reconstitution of the PGE receptor with pure Gam, Gi, or Go in phospholipid vesicles resulted in a remarkable restoration of [3H]PGE2 binding activity in a GTP-dependent manner. The efficiency of these three G-proteins in this capacity was roughly equal. When pertussis toxin- or N-ethylmaleimide-treated G-proteins, instead of the native ones, were reconstituted into vesicles, the restoration of binding activity was no longer observed. The displacement of [3H]PGE2 binding was specific for PGE1 and PGE2. Furthermore, addition of PGE2 stimulated the GTPase activity of the G-proteins in reconstituted vesicles. These results indicate that the PGE receptor can couple functionally with Gam, Gi, or Go in phospholipid vesicles and suggest that Gam may be involved in signal transduction of the PGE receptor in bovine adrenal medulla.
...
PMID:Functional reconstitution of prostaglandin E receptor from bovine adrenal medulla with guanine nucleotide binding proteins. 289

Urinary prostaglandin E (UPGE) excretion increased significantly after 1 and 2 wk of potassium depletion (KD) in female New Zealand White rabbits on ad libitum water intake [UPGE control, 21.3 +/- 4.6 ng PGE/mg creatinine; 1 wk KD, 40.4 +/- 6.1 ng PGE/mg creatinine (P less than 0.01); 2 wk KD, 31.9 +/- 14.9 ng PGE/mg creatinine (P less than 0.05)]. In vivo prostaglandin inhibition with indomethacin or meclofenamate significantly increased urinary osmolality after 12 h of dehydration and exogenous vasopressin (1.25 U) from 794 +/- 59 to 1,163 +/- 113 mosmol/kgH2O (P less than 0.01). In vitro prostaglandin inhibition with indomethacin or meclofenamate corrected the antidiuretic hormone (ADH) unresponsiveness of isolated perfused cortical collecting tubules (CCTs) from KD rabbits. Furthermore, preincubation with pertussis toxin, an agent that inactivates the guanine nucleotide inhibitory (Ni) subunit of adenylate cyclase, normalized the ADH response of KD CCTs, suggesting that prostaglandins may attenuate ADH action on the CCT through activation of Ni and contribute to the urinary concentrating defect associated with KD.
...
PMID:Prostaglandins and the urinary concentrating defect in potassium-depleted rabbits. 342 21

Bordetella pertussis culture fractions produce decreased metabolic responses to isoproterenol and epinephrine in mice and rats, suggesting the possibility of systemic beta adrenergic blockade. The present study was undertaken to elucidate the mechanism of the alteration in adrenergic responsiveness and to clarify its relationship to other biological effects of the organism. Lymphocytes were selected as a suitable tissue because of the marked alteration in lymphocyte distribution in pertussis-treated mice and rats, suggesting a change in the surface properties of these cells. Human peripheral blood lymphocytes, purified by nylon fiber chromatography, were studied. In short incubation experiments (20 min or less) B. pertussis did not alter the cyclic AMP response to isoproterenol, prostaglandin E (PGE(1)), or methacholine. However, when cells were preincubated with B. pertussis for 90 min at 37 degrees C, the responses to all three agents were markedly inhibited. Although these observations provide direct confirmation of the ability of B. pertussis to inhibit catecholamine responsiveness, the fact that PGE(1) and methacholine responses were also inhibited suggests that blockade at the level of the beta adrenergic receptor is doubtful. The inhibitory activity was localized in a nondialyzable, protein-rich fraction that is precipitated from B. pertussis culture fluid by ammonium sulfate at 90% of saturation. The bulk of the activity was obtained in the load volume after 50,000 g centrifugation in a cesium chloride gradient, density 1.2-1.5 (fraction 4). Fraction 4 produced a change in lymphocyte hormonal responsiveness at concentrations as low as 5 ng/ml. The relationship between cyclic AMP inhibitory activity in isolated human cells and leukocytosis-producing activity in intact mice was studied. The two activities seemed to parallel one another quite closely until the final Sephadex G-150 fractionation step, in which the two activities were obtained in the same column fraction, but a greater recovery of the leukocytosis-producing activity was obtained. Additional purification will be required to establish conclusively whether the same macromolecule is responsible for both activities. The availability of a bacterial product that markedly inhibits cyclic AMP accumulation in purified lymphocytes may help to clarify the role of cyclic AMP in lymphocyte activation by antigen and nonspecific mitogens.
...
PMID:The effect of Bordetella pertussis on lymphocyte cyclic AMP metabolism. 434 77

Interleukin 3-dependent BNu-2cl3 mast cells, mucosal type-like mast cells, exhibited a specific high-affinity binding site for [3H]prostaglandin (PG) E2. The binding was completely displaced by M&B 28767, an EP3-selective agonist, but not by EP1- or EP2-selective ligands, indicating that the PGE2 binding site is of the EP3 subtype PGE receptor. Whereas the EP3 subtype is presumed to be coupled to inhibition of adenylate cyclase in various tissues and cells, in BNu-2cl3 cells PGE2 had no ability to inhibit adenylate cyclase activity, while it induced concentration-dependent stimulation of phosphoinositide metabolism and caused an increase in the intracellular free Ca2+ concentration in a pertussis toxin-sensitive manner. PGE2 by itself did not evoke histamine release from the cells, but it markedly stimulated histamine release in concert with ionomycin, a Ca2+ ionophore. The PGE2-stimulated release was also completely blocked by pertussis toxin. Thus, the PGE receptor expressed on BNu-2cl3 mast cells is of the EP3 subtype and is linked to phosphoinositide metabolism via a pertussis toxin-sensitive G protein, and this activation leads to histamine release.
...
PMID:Characterization of the prostaglandin E receptor expressed on a cultured mast cell line, BNu-2cl3. 769 May 67

Thromboxane A2 (TXA2), the major cyclooxygenase (COX) product of arachidonic acid (AA), activates platelets and is a potent vasoconstrictor. The functional importance of this eicosanoid has been demonstrated in syndromes of acute coronary ischaemia. The cellular response to this agonist is tightly regulated. The liberation of AA from membrane phospholipids is conventionally thought to be the rate limiting step in TXA2 biosynthesis. However, the discovery of a second, highly regulated COX gene (COX-2) and the demonstration of product-based inactivation of COX and thromboxane synthase suggest a more complex regulation of TXA2 formation. TXA2 signalling is mediated by a G-protein linked receptor (PGH2/TXA2 receptor) which activates phospholipase C (PLC). Pharmacological studies suggest two distinct binding sites on platelets, but receptor heterogeneity has yet to be documented at a molecular level. The PGH2/TXA2 receptors are linked via a pertussis and cholera toxin-insensitive G-protein which has not been fully characterized, but is thought to belong to the Gq class of G-proteins. The diversity of G-protein alpha subunits, and growing evidence suggesting functional roles for the beta-gamma subunit, support a possible dual signalling mechanism of cellular activation. This may be of particular importance in regulating the response to eicosanoids with contrasting actions. A receptor for prostacyclin (PGI2) has not yet been cloned but biochemical studies suggest that it is linked to the activation of adenylate cyclase via Gs. At least three distinct prostaglandin E receptors have been identified. Desensitization of the cellular responses to the activation of TXA2, PGI2 and PGE receptors have been demonstrated and potential phosphorylation sites in their COOH terminal ends may be important in mediating this effect.
...
PMID:Cellular activation by thromboxane A2 and other eicosanoids. 813 96

1. The present study examines the effect of naturally occurring prostanoids and prostaglandin (PG) congeners on gastrin- and pituitary adenylate cyclase-activating peptide (PACAP)-evoked histamine and pancreastatin secretion from isolated rat stomach ECL cells. 2. ECL cells (75-85% purity) were isolated from rat stomach using pronase digestion followed by repeated counter-flow elutriation and cultured for 48 h before secretion experiments. The release of histamine and pancreastatin was determined by radioimmunoassay. 3. None of the PGs tested stimulated the release of either histamine or pancreastatin. 4. PGE1 and PGE2 inhibited both gastrin- and PACAP-evoked histamine and pancreastatin secretion (IC50 = 1-2 x 10(-10) M). Most other naturally occuring prostanoids and PG congeners had no or little inhibitory effect. The PGE analogues misoprostol and sulprostone were more potent (IC50 = 0.9 x 10(-11) M and 2 x 10(-11) M respectively) than PGE1 and PGE2. The rank order of potency was misoprostol > sulprostone > PGE1 = PGE2, suggesting the involvement of the so-called EP3 receptor. 5. The effects of PGs on the stomach ECL cells may be direct or indirect, for instance through the stimulated release of somatostatin from contaminating D cells (2-3%). However, the amount of somatostatin in the cell culture after 48 h was below the limit of detection, and somatostatin immunoneutralization did not prevent misoprostol from inhibiting secretion from the ECL cells. 6. The misoprostol-induced inhibition was reversed by pertussis toxin suggesting the involvement of G-protein subunits G alpha(0) and/or G alpha(i). 7. In view of the potency by which PGE1, PGE2, misoprostol and sulprostone inhibited the stimulated release of histamine and pancreastatin, we suggest that the ECL cells represent a primary target for prostaglandins acting via an EP3 receptor in the oxyntic mucosa. 8. The results suggest that the clinically useful effect of misoprostol as an anti-ulcer drug reflects its ability to inhibit stomach ECL-cell histamine secretion.
...
PMID:Prostaglandins inhibit secretion of histamine and pancreastatin from isolated rat stomach ECL cells. 972 Aug 5

The effects of PGE2 on voltage-dependent Ca2+ channel currents were studied in dissociated rat melanotrophs by the whole-cell configuration of the patch-clamp technique. In about 90% of melanotrophs examined, PGE2 reversibly inhibited voltage-dependent Ba2+ currents elicited by voltage steps from a holding potential of -80 to 0 mV, with an ED50 of 68 nM. The maximum inhibition of Ba2+ currents by 1 microM PGE2 (35.3%) was comparable with that by the maximally effective concentration (100 nM) of dopamine. The EP1/EP3 PGE (EP) agonists, 17PT-PGE2 and sulprostone, and the EP2/EP3 agonist, misoprostol, mimicked the inhibition by PGE2, whereas the selective EP2 agonist, butaprostol, had little effect. The inhibition by PGE2 was partially, but significantly, reduced by the selective EP1 antagonist, SC-51322. The magnitude of the PGE2-induced inhibition of Ba2+ currents was greatly reduced by pretreatment with pertussis toxin, or by a depolarizing prepulse, to +80 mV, lasting for 50 msec. Although four distinct types (N-, P/Q-, L-, and R-types) of high-threshold Ba2+ currents were observed, PGE2 (1 microM) caused significant inhibition of only P/Q- and L-type currents, which were 17.3 and 10.1%, respectively, of the total Ba2+ currents. These results suggest that PGE2 inhibits P/Q- and L-type Ca2+ channels of rat melanotrophs via EP1 and EP3 receptors, which are coupled to pertussis toxin-sensitive G proteins, and produces both voltage-sensitive and -insensitive inhibition of Ca2+ channels.
...
PMID:Inhibition of voltage-dependent calcium channels by prostaglandin E2 in rat melanotrophs. 983 16

Prostaglandin E(1) (PGE(1)) has cardioprotective effects on the ischemic-reperfused heart. To clarify the mechanisms underlying the protective action of PGE(1) on myocardium, we examined the effect of PGE(1) on the L-type Ca(2+) current (I(Ca)) using single atrial cells from rabbits. PGE(1) did not show a significant effect on basal I(Ca) but inhibited the I(Ca) prestimulated by isoproterenol (Iso, 30 nM). This inhibition was concentration dependent (EC(50) = 0.027 microM). Both sulprostone, a specific PGE receptor subtype (EP(1) and EP(3)) agonist, and 11-deoxy-PGE(1), an EP(3) agonist, inhibited the Iso-stimulated I(Ca), similar to PGE(1). Pretreatment with pertussis toxin (PTX) abolished the PGE(1) inhibition of I(Ca). Both the application of forskolin plus IBMX and intracellular dialysis with 8-bromoadenosine 3',5'-cyclic monophosphate eliminated the effect of PGE(1). PGE(1) did not show any further inhibition of I(Ca) when the effect of Iso was almost fully antagonized by acetylcholine. Methylene blue (guanylate cyclase inhibitor), KT-5823 (cGMP-dependent protein kinase inhibitor), and erythro-9-(2-hydroxy-3-nonyl)adenine (type II phosphodiesterase inhibitor) did not significantly change the inhibitory effect of PGE(1). These findings suggest that 1) PGE(1) inhibits Iso-stimulated I(Ca) by binding to the EP(3) receptor and 2) the PTX-sensitive and cAMP-dependent pathway is involved in the PGE(1) inhibition of I(Ca), but the nitric oxide-cGMP-dependent pathway is not. The PGE(1)-induced antiadrenergic effect shown in this study may contribute to the PGE(1) protection of myocardium against ischemia.
...
PMID:EP receptor-mediated inhibition by prostaglandin E(1) of cardiac L-type Ca(2+) current of rabbits. 1051 71

The adrenal gland contains resident macrophages, some of which lie adjacent to the catecholamine producing chromaffin cells. Because macrophages release a variety of secretory products, it is possible that paracrine signaling between these two cell types exists. Of particular interest is the potential paracrine modulation of voltage-gated calcium channels (I(Ca)), which are the main calcium influx pathway triggering catecholamine release from chromaffin cells. We report that prostaglandin E(2) (PGE(2)), one of the main signals produced by macrophages, inhibited I(Ca) in cultured bovine adrenal chromaffin cells. The inhibition is rapid, robust, and voltage dependent; the activation kinetics are slowed and inhibition is largely reversed by a large depolarizing prepulse, suggesting that the inhibition is mediated by a direct G-protein betagamma subunit interaction with the calcium channels. About half of the response to PGE(2) was sensitive to pertussis toxin (PTX) incubation, suggesting both PTX-sensitive and -insensitive G proteins were involved. We show that activation of macrophages by endotoxin rapidly (within minutes) releases a signal that inhibits I(Ca) in chromaffin cells. The inhibition is voltage dependent and partially PTX sensitive. PGE(2) is not responsible for this inhibition as blocking cyclooxygenase with ibuprofen did not prevent the production of the inhibitory signal by the macrophages. Nor did blocking the lipoxygenase pathway with nordihydroguaiaretic acid alter production of the inhibitory signal. Our results suggest that macrophages may modulate I(Ca) and catecholamine secretion by releasing PGE(2) and other chemical signal(s).
...
PMID:Evidence for paracrine signaling between macrophages and bovine adrenal chromaffin cell Ca(2+) channels. 1063 71

<< Previous 1 2 3 4 5 6 7 Next >>