UMLS:C0043167 - FACTA Search

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

Dopamine receptors of D2 type present on lactotroph cells are coupled to a large series of transduction mechanisms. Beside their negative coupling with adenylate cyclase, they are also coupled with potassium and calcium channels, leading to a decreased intracellular calcium concentration. In addition, D2 dopamine receptors also modulate phospholipase activities. Dopamine inhibits inositol phosphate production, through two distinct mechanisms. One of them could represent a direct negative coupling with phospholipase C. All these transduction mechanisms of the D2 dopamine receptors implicate G proteins sensitive to pertussis toxin. In contrast, these receptors are negatively coupled to phospholipase A2 through G proteins insensitive to this toxin. Both isoforms of the D2 dopamine receptor, generated by alternate splicing of a single gene, are present in lactotroph cells. After transfection in CH4C1 cells the two isoforms are coupled with adenylate cyclase while only the shortest isoform appears negatively coupled to phospholipase C. Functional D2 dopamine receptors are present in human prolactinomas. Resistance to bromocriptine therapy is associated with a decreased density of these receptors in the tumor. In addition, the ratio of the two receptor isoforms (measured by PCR) is different in responsive and resistant tumors. Furthermore, the activity of Gi/Go proteins coupled to adenylate cyclase appears also affected in resistant tumors. Resistance to bromocriptine therapy appears thus to involve multiple changes at the different levels of the multiple mechanisms of action of dopamine on lactotroph cells.
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PMID:D2 dopaminergic receptors: normal and abnormal transduction mechanisms. 130 22

Two amphiphilic peptides from hymenopterid insects, melittin and mastoparan, stimulate secretion in a variety of cell types. In PC12 cells, both peptides stimulate calcium influx with melittin some 20-fold more potently than mastoparan. Melittin stimulates both breakdown of phosphoinositides (Pl) by phospholipase C to yield inositol phosphates and hydrolysis of phospholipids by phospholipase A2 to release arachidonic acid (AA). Mastoparan stimulates Pl breakdown, but has no effect on AA release. Maximal stimulation of Pl breakdown occurs at 1 to 2.5 micrograms/ml melittin and 30 micrograms/ml mastoparan, whereas maximal stimulation of AA release occurs at 2 to 5 micrograms/ml melittin. Organic calcium channel blockers (nifedipine, verapamil, diltiazem) have little or no effect on responses to the peptides. The influx of calcium elicited by melittin or mastoparan is completely or nearly completely blocked by inorganic calcium channel blockers (Co++, Mn++, Cd++). Mn++ and Cd++ inhibit melittin-induced Pl breakdown and AA release and mastoparan-induced Pl breakdown. Co++ has no effect on melittin-induced Pl breakdown and potentiates mastoparan-induced Pl breakdown. Pertussis toxin has no effect on the Pl breakdown induced by either peptide. The responses to melittin and mastoparan in PC12 cells are compared to those reported for maitotoxin.
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PMID:Effects of the amphiphilic peptides melittin and mastoparan on calcium influx, phosphoinositide breakdown and arachidonic acid release in rat pheochromocytoma PC12 cells. 130 80

We previously reported that pertussis toxin (PTX)-sensitive GTP-binding protein is involved in the coupling of prostaglandin E2 (PGE2) receptor to phospholipase C in osteoblast-like MC3T3-E1 cells (1). In the present study, we analyzed the mechanism of PGE2-induced arachidonic acid (AA) release in MC3T3-E1 cells. PGE2 stimulated the release of AA and the formation of inositol trisphosphate (IP3) dose dependently in the range between 1 nM and 10 microM. The effect of PGE2 on AA release (ED50 was 80 nM) was more potent than that on IP3 formation (ED50 was 0.8 microM). Quinacrine, a phospholipase A2 inhibitor, suppressed the PGE2-induced AA release but had little effect on the IP3 formation. NaF, a GTP-binding protein activator, mimicked PGE2 by stimulating the AA release. The AA release stimulated by a combination of PGE2 and NaF was not additive. PTX had little effect on the PGE2-induced AA release. These results strongly suggest that the AA release and the phosphoinositide hydrolysis are separately stimulated by PGE2 in osteoblast-like cells, and the PGE2-induced AA release is mediated by PTX-insensitive GTP-binding protein.
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PMID:Mechanism of prostaglandin E2-induced arachidonic acid release in osteoblast-like cells: independence from phosphoinositide hydrolysis. 132 13

We have previously reported that platelet-activating factor (PAF) elevates cytosolic free calcium concentration ([Ca2+]i) in fura-2-loaded glomerular mesangial cells. To confirm that this increase in [Ca2+]i is a result of receptor-mediated activation of phospholipase C, we investigated hydrolysis of phosphatidylinositol-4,5-bisphosphate (PtdIns-4,5-P2) in PAF-treated mesangial cells. PAF (10(-7) M) stimulated a rapid and transient formation of inositol trisphosphate. In concomitant experiments, PAF stimulated a biphasic accumulation of 3H-arachidonate-labeled 1,2-diacylglycerol (DAG). The secondary elevation in DAG was coincident with a rise in 3H-phosphorylcholine (PC) and 3H-phosphorylethanolamine (PE) suggesting that PAF stimulates delayed phospholipase activities which hydrolyze alternate phospholipids besides the polyphosphoinositides. This PAF-stimulated elevation in 3H-water soluble phosphorylbases was seen at 5 min but not at 15 sec suggesting that the initial rise in DAG as well as the initial elevation in [Ca2+]i are due primarily to PtdIns-4,5-P2 hydrolysis. PAF also stimulated PGE2 as well as 3H-arachidonic acid and 3H-lyso phosphatidylcholine (PtdCho) formation. We suggest that arachidonate released specifically from PtdCho via phospholipase A2 is a source of this PAF-elevated PGE2. It has been postulated that anti-inflammatory prostaglandins may antagonize the contractile and proinflammatory effects of PAF via activation of adenylate cyclase. Surprisingly, exogenous PAF reduced basal and receptor-mediated cAMP concentration indicating that PAF-stimulated transmembrane signaling pathways may oppose receptor-mediated activation of adenylyl cyclase. We have taken advantage of the different sensitivities of phospholipases A2 and C(s) to PMA, EGTA, and pertussis toxin to dissociate phospholipase A2 and C activities. Acute PMA-treatment enhanced PAF-stimulated PGE2 formation, reduced PAF-induced elevations in [Ca2+]i and had no effect upon PAF-stimulated 3H-PE. We have also demonstrated that phospholipase A2, but not PtdIns-specific phospholipase C, was sensitive to external calcium concentration. The role of a GTP-binding protein to couple PAF-receptors to the PtdIns-specific phospholipase C was confirmed as GTP gamma S synergistically elevated PAF-stimulated inositol phosphate formation. We also demonstrated that pertussis toxin ADP-ribosylates a single protein of an apparent 42 kD mass and that PAF pretreatment reduced subsequent ADP-ribosylation in a time-dependent manner. However, pertussis toxin had no effect upon phospholipase C-generated water soluble phosphorylbases or inositol phosphates. In contrast, PAF-stimulated phospholipase A2 and PAF-inhibited adenylyl cyclase activities were sensitive to pertussis toxin.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Platelet-activating factor stimulates multiple signaling pathways in cultured rat mesangial cells. 133 Nov 21

To evaluate the identity of the guanosine triphosphate--binding proteins coupling arginine vasopressin receptor occupancy with activation of phospholipase C, leading to Ca2+ mobilization, and activation of phospholipase A2, leading to arachidonate release and prostanoid formation, we used intact cells, saponin-permeabilized cells, and membranes of the rat mesangial cell. Arginine vasopressin 10(-7) mol/L produced a dose-dependent increase in cytosolic Ca2+ to maximal levels of 500 nmol/L with peak responses occurring within 10 seconds of addition of arginine vasopressin to cells in suspension. Arginine vasopressin 10(-7) mol/L elicited a maximal response. These increases were associated temporarily with a fourfold increase in tritiated D-myo-inositol 1,4,5-trisphosphate formation in prelabeled cells. Pertussis toxin (200 ng/ml) did not inhibit the Ca2+ increase nor did it inhibit the increase in tritiated D-myo-inositol 1,4,5-trisphosphate formation, suggesting a pertussis toxin--insensitive signaling pathway for phospholipase C hydrolysis in response to vasopressin. Membranes prepared from mesangial cells increased D-myo-inositol 1,4,5-trisphosphate formation in vitro in response to arginine vasopressin and guanosine-5'-0(3- thiotrisphosphate), and this stimulation was inhibited by guanosine-5'-0(2-thiodiphosphate), confirming the involvement of a guanosine triphosphate--binding protein. In contrast arginine vasopressin stimulated arachidonate release from intact mesangial cells, and this effect was blocked by pretreating cells with pertussis toxin. To demonstrate that this was through a pertussis toxin--sensitive guanosine triphosphate--binding protein, we permeabilized cells with saponin and determined that arginine vasopressin and guanosine-5'-0(3-thiotriphosphate) stimulated the release of arachidonic acid and the stimulation of guanosine-5'-0(3-thiotriphosphate) was inhibited by guanosine-5'-0(2-thiodiphosphate). Finally, pertussis toxin was able to stimulate adenosine diphosphate ribosylation in vivo of a substrate protein in mesangial cell membranes of 41 kd, and this ribosylation was inhibited by pretreating cells with pertussis toxin. These data suggest that the release of arachidonic acid by vasopressin in glomerular mesangial cells is linked to a pertussis toxin--sensitive guanosine triphosphate--binding protein and that this activation of phospholipase C in vasopressin is linked to a pertussis toxin--insensitive guanosine triphosphate--binding protein.
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PMID:Different guanosine triphosphate-binding proteins couple vasopressin receptor to phospholipase C and phospholipase A2 in glomerular mesangial cells. 133 Dec 76

We recently reported that prostaglandin E2 (PGE2) and arachidonic acid (AA) each induced a gradual secretion of catecholamines from cultured bovine adrenal chromaffin cells in the presence of ouabain by stimulation of phosphoinositide metabolism. In the present study, we examined the relationship between phospholipase A2 and C activation and catecholamine secretion by PGE2 in chromaffin cells. The phospholipase A2 inhibitors p-bromophenacyl bromide and mepacrine did not affect the basal and ouabain-induced release, but dose-dependently blocked PGE2-evoked phosphoinositide metabolism and the consequent catecholamine release at an IC50 value of 3 microM. PGE2 induced rapid hydrolysis of [3H]AA from prelabeled phospholipid pools: the release of [3H]AA could be detected at as early as 15 sec and reached a plateau after 1 min. While the phospholipase C inhibitor neomycin did not inhibit PGE2-induced AA release, phospholipase A2 inhibitors dose-dependently inhibited it at IC50 values comparable to those for catecholamine release. Pretreatment of intact cells with the phorbol ester 12-O-tetradecanoylphorbol 13-acetate, but not with pertussis toxin, prevented AA release by PGE2. These results demonstrate that PGE2 activates phospholipase A2 as well as phospholipase C in a pertussis toxin-insensitive manner and suggest that the released arachidonic acid may be involved in PGE2-induced catecholamine release from chromaffin cells.
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PMID:Prostaglandin E2-induced arachidonic acid release and catecholamine secretion from cultured bovine adrenal chromaffin cells. 133 53

In cultured striatal astrocytes, 2-chloroadenosine, an adenosine analog resistant to adenosine deaminase, although inactive alone, markedly potentiated the activation of phospholipase C induced by methoxamine, an alpha 1-adrenergic agonist. This effect was suppressed by antagonists of either A1 adenosine or alpha 1-adrenergic receptors. An influx of calcium and two distinct G-proteins are involved in this phenomenon since the potentiating effect of 2-chloradenosine was suppressed in the absence of external calcium or when cells were pretreated with pertussis toxin. In addition, arachidonic acid is likely involved in this potentiating effect. This was shown first by examining the effects of inhibitors of phospholipase A2 or arachidonic metabolism, then by examining the action of arachidonic acid on the production of inositol phosphates in either the presence or absence of methoxamine, and finally by measuring the release of arachidonic acid. The sequential activation of phospholipase C and of protein kinase C is required for the 2-chloroadenosine-induced activation of phospholipase A2 since 2-chloroadenosine markedly stimulated phospholipase C activity in the absence of methoxamine when protein kinase C was activated by a diacylglycerol analog. Finally, the enhancing effect of 2-chloroadenosine on the methoxamine-evoked response seems to result from an inhibition of glutamate reuptake into astrocytes by arachidonic acid. Indeed, the potentiating effect of 2-chloroadenosine was suppressed when external glutamate was removed enzymatically and mimicked by either selective inhibitors of the glutamate reuptake process or direct application of glutamate.
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PMID:2-Chloroadenosine potentiates the alpha 1-adrenergic activation of phospholipase C through a mechanism involving arachidonic acid and glutamate in striatal astrocytes. 134 73

Transmembrane signalling mechanisms of tumor necrosis factor alpha (TNF alpha) were examined with special reference to the involvement of G-protein, in intact and permeabilized murine osteoblast-like cells. TNF alpha stimulated the release of 3H radioactivity from intact cells labeled with [3H]arachidonic acid within 10 min in a dose dependent manner and the production of lyso forms of phospholipids, an event presumably mediated through the activation of phospholipase A2. Production of cAMP and inositol 1,4,5-trisphosphate was not affected by TNF alpha. Pretreatment of the cells with pertussis toxin inhibited the liberation of [3H]arachidonate. GTP gamma S (guanosine 5'-3-O-(thio)triphosphate) reduced the binding affinity of [125I]TNF alpha to beta-escin-permeabilized cells. The addition of TNF alpha together with an unhydrolyzable analog of GTP, GTP gamma S, to the beta-escin-permeabilized cells prelabeled with [3H]arachidonic acid led to a release of the 3H radioactivity. The production of prostaglandin E2 (PGE2) was markedly stimulated by TNF alpha in a dose over 100 ng/ml, with a latent time of about 3 h, and the stimulation was abolished by pretreatment with pertussis toxin. The time and dose requirements for this process differed from those for the possible activation of phospholipase A2, thereby indicating that other process(es) in addition to the activation of phospholipase A2 may be responsible for the enhanced production of PGE2. The activity of cyclooxygenase (i.e. the combined activities of prostaglandin endoperoxide syntase and PGH2-PGE2 isomerase) was stimulated by TNF alpha with much the same time and dose requirements as for the production of PGE2, and the activation was found to be due to the increased amount of the enzyme, as assessed by a Western blot analysis with anti-cyclooxygenase antibody. This process was also sensitive to pertussis toxin. Therefore, receptors for TNF alpha in MC3T3-E1 cells apparently couple to G-protein sensitive to pertussis toxin and the coupling regulates the activations of phospholipase A2 and the de novo synthesis of cyclooxygenase.
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PMID:Signal transduction by tumor necrosis factor alpha is mediated through a guanine nucleotide-binding protein in osteoblast-like cell line, MC3T3-E1. 137 94

The N-methyl-D-aspartate (NMDA)-sensitive subtype of glutamate receptor, which gates Ca(2+)-permeable ion channels, is known for its role in learning and memory formation, in the induction of long-term potentiation, and also in seizure activity and neurotoxicity. In primary cultures of cerebellar neurons, agonists of NMDA receptors induce a dose-dependent release of [3H]arachidonic acid ([3H]AA), which is potentiated by activation of the glycine-positive modulatory site and inhibited by NMDA receptor antagonists. NMDA receptor-induced [3H]AA release is inhibited by quinacrine and partially depends on the presence of extracellular calcium. The [3H]AA release is not sensitive, however, to pretreatment with pertussis or cholera toxin, which suggests a Ca(2+)-dependent activation of phospholipase A2 not employing G proteins. Pretreatment of cultures with the natural and semisynthetic sphingolipids GT1b and PKS 3, respectively, inhibits NMDA receptor-mediated [3H]AA release. We also demonstrated glutamate-evoked [3H]AA release from rat hippocampal slices, which is NMDA receptor mediated, calcium dependent and sensitive to quinacrine. Arachidonic acid and its metabolites have been shown to play a role as second messengers and to modulate neuronal activity. Moreover, they are thought to act as transsynaptic modulators in the mechanism of NMDA receptor-induced long-term potentiation in the hippocampus. Their role in ischemic brain pathology has also been postulated. Our experiments on cultured cerebellar granule cells, incubated in a Mg(2+)-free medium deprived of glucose and oxygen, demonstrated a time-dependent stimulation of [3H]AA release. This release was inhibited by antagonists of NMDA receptors and by quinacrine. Stimulation of NMDA-sensitive glutamate receptors and the subsequent calcium-mediated activation of phospholipase A2 may play a role in the in vivo release of arachidonic acid during brain ischemia. This hypothesis is supported by the observation that the enhanced level of thromboxane B2 in the gerbil brain after 5 min of global ischemia is reduced by the systemic application of either the NMDA antagonist MK-801 or the ganglioside GM1.
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PMID:NMDA receptor-mediated arachidonic acid release in neurons: role in signal transduction and pathological aspects. 138 78

Although several cytokines have been demonstrated to exert pleiotropic responses, there is little information on cytokine regulation of renal tubular epithelial cell function. In the present studies, we find that both T cell-derived (tumor necrosis factor-beta and interleukins 2 and 3) and monocyte/macrophage derived (tumor necrosis factor alpha and interleukin 1 beta) cytokines promote basal, arginine vasopressin- and forskolin-stimulated adenylate cyclase activity in cultured LLC-PK1 cells. No effect of TNF, IL-1 beta, and IL-2 to stimulate protein kinase C activity was observed. TNF-beta, IL-1 beta and IL-2 also modestly stimulated 3H release from 3H-arachidonic acid labeled cells. Mepacrine, a phospholipase A inhibitor, prevented TNF-beta stimulation of 3H release from 3H-arachidonic acid labeled cells and TNF-beta potentiation of adenylate cyclase activity. TNF-beta potentiation of adenylate cyclase activity and stimulation of 3H release from 3H arachidonic acid labeled cells was not prevented by pertussis toxin. These results demonstrate that several cytokines can stimulate adenylate cyclase activity while not affecting protein kinase C activity in cultured renal tubular epithelial cells. The effect of TNF-beta to stimulate adenylate cyclase appears to occur independent of pertussis toxin-sensitive substrate and may involve activation of phospholipase A.
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PMID:Cytokine regulation of adenylate cyclase activity in LLC-PK1 cells. 140 34

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