Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Flufenamic Acid”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 811 records · Page 45Linked to original sources
PubMed2003

TRPC5 as a candidate for the nonselective cation channel activated by muscarinic stimulation in murine stomach.

We investigated which transient receptor potential (TRP) channel is responsible for the nonselective cation channel (NSCC) activated by carbachol (CCh) in murine stomach with RT-PCR and the electrophysiological method. All seven types of TRP mRNA were detected in murine stomach with RT-PCR. When each TRP channel was expressed, the current-voltage relationship of mTRP5 was most similar to that recorded in murine gastric myocytes. mTRP5 showed a conductance order of Cs(+) > K(+) > Na(+), similar to that in the murine stomach. With 0.2 mM GTPgammaS in the pipette solution, the current was activated transiently in both NSCC in the murine stomach and the expressed mTRP5. Both NSCC activated by CCh in murine stomach and mTRP5 were inhibited by intracellularly applied anti-G(q/11) antibody, PLC inhibitor U-73122, IICR inhibitor 2-aminoethoxydiphenylborate, and nonspecific cation channel blockers La(3+) and flufenamate. There were two other unique properties. Both the native NSCC and mTRP5 were activated by 1-oleoyl-2-acetyl-sn-glycerol. Without the activation of NSCC by CCh, the NSCC in murine stomach was constitutively active like mTRP5. From the above results, we suggest that mTRP5 might be a candidate for the NSCC activated by ACh or CCh in murine stomach.

Animals↗
PubMed1999

Evidence for Gd(3+) inhibition of membrane ATP permeability and purinergic signaling.

Extracellular ATP functions as an important autocrine and paracrine signal that modulates a broad range of cell and organ functions through activation of purinergic receptors in the plasma membrane. Because little is known of the cellular mechanisms involved in ATP release, the purpose of these studies was to evaluate the potential role of the lanthanide Gd(3+) as an inhibitor of ATP permeability and to assess the physiological implications of impaired purinergic signaling in liver cells. In rat hepatocytes and HTC hepatoma cells, increases in cell volume stimulate ATP release, and the localized increase in extracellular ATP increases membrane Cl(-) permeability and stimulates cell volume recovery through activation of P(2) receptors. In cells in culture, spontaneous ATP release, as measured by a luciferin-luciferase-based assay, was always detectable under control conditions, and extracellular ATP concentrations increased 2- to 14-fold after increases in cell volume. Gd(3+) (200 microM) inhibited volume-sensitive ATP release by >90% (P < 0.001), inhibited cell volume recovery from swelling (P < 0.01), and uncoupled cell volume from increases in membrane Cl(-) permeability (P < 0.01). Moreover, Gd(3+) had similar inhibitory effects on ATP release from other liver and epithelial cell models. Together, these findings support an important physiological role for constitutive release of ATP as a signal coordinating cell volume and membrane ion permeability and suggest that Gd(3+) might prove to be an effective inhibitor of ATP-permeable channels once they are identified.

Adenosine Triphosphate↗
PubMed1998

Inhibition of amiloride-sensitive sodium-channel activity in distal lung epithelial cells by nitric oxide.

Distal lung epithelial cells (DLECs) play an active role in fluid clearance from the alveolus by virtue of their ability to actively transport Na+ from the alveolus to the interstitial space. The present study evaluated the ability of activated macrophages to modulate the bioelectric properties of DLECs. Low numbers of lipopolysaccharide (LPS)-treated macrophages were able to significantly reduce amiloride-sensitive short-circuit current (Isc) without affecting total Isc or monolayer resistance. This was associated with a rise in the flufenamic acid-sensitive component of the Isc. The effect was reversed by the addition of N-monomethyl-L-arginine to the medium, implying a role for nitric oxide. We hypothesized that macrophages exerted their effect by expressing inducible nitric oxide synthase (iNOS) in DLECs. The products of LPS-treated macrophages increased the levels of iNOS protein and mRNA transcripts in DLECs as well as causing a rise in iNOS activity. Immunofluorescence microscopy of LPS-stimulated macrophage-DLEC cocultures with anti-nitrotyrosine antibodies provided evidence for the generation of peroxynitrite in macrophages but not in DLECs. These data indicate that activated macrophages in the lung may contribute to impaired resolution of acute respiratory distress syndrome and suggest a novel mechanism whereby nitric oxide might alter cell function by altering its ion-transporting phenotype.

Amiloride↗
PubMed2006

Inhibition of hypertonicity-induced cation channels sensitizes HeLa cells to shrinkage-induced apoptosis.

Hypertonicity-induced cation channels (HICCs) are an effective mechanism of regulatory volume increase (RVI), which is a restoration process of cell volume after osmotic cell shrinkage, in HeLa cells. Since a reduction of cell size is a hallmark of programmed cell death, we tested whether a blockage of HICCs sensitizes HeLa cells to shrinkage-induced apoptosis by using proliferation assays, apoptosis assays, and patch-clamp recordings. Under control conditions, increasing osmolality up to 600 mosmol/kg-H2O had no detectable effect on either cell proliferation or apoptosis. With HICCs blocked by flufenamate and Gd3+, however, a significant reduction of proliferation and a stimulation of apoptosis were observed. Both effects exhibited virtually identical sensitivity profiles to osmotic stress as well as to flufenamate and Gd3+. Moreover, the observed concentration dependency of flufenamate and Gd3+ on proliferation and apoptosis was in excellent accordance with that on HICC inhibition. These results suggest that persistent cell shrinkage may function as a specific signal in the induction of apoptosis. In addition, they provide further evidence for the interplay of proliferation vs. apoptosis and the actual role that mechanisms of cell volume regulation do play in these processes.

Apoptosis↗
PubMed1977

Elimination of inhibition in euglobulin fibrinolysis by use of flufenamate: involvement of C1-inactivator.

The fibrinolytic activity of euglobulin fractions prepared from human morning plasma and assayed on fibrin plates is strongly inhibited by the C1-inactivator present in the fractions. Flufenamate, a potent representative of the group of synthetic thrombolytic agents, eliminates this inhibition in euglobulin fractions. This elimination is an apparently irreversible reaction dependent on concentration, time and temperature. The fibrinolytic enhancing effect of flufenamate in euglobulin fractions correlated well with a similar effect of added C1s, which neutralized the C1-inactivator. The effect of flufenamate was slightly greater than that of added C1s, suggesting an additional effect of the flufenamate. The activity enhancing effect of the flufenamate at the lower molarities could be separated from an activity decreasing effect at the higher molarities. A simple technique by which inhibitory effects in euglobulin fibrinolysis are selectively eliminated is described.

Complement C1 Inactivator Proteins↗
PubMed1981

Generation of fibrinolytic activity in bovine plasma by the combined effects of chloroform and dextran sulphate.

Bovine plasma yields fibrinolytically inactive euglobulin fractions, even when prepared in the presence of dextran sulphate. Addition of flufenamate to these solutions only occasionally elicits a slight activity. However, highly fibrinolytic solutions are produced when euglobulins precipitated in the presence of dextran sulphate are exposed to chloroform. Evidence indicates that a plasminogen activator is formed, which subsequently converts plasminogen present in the fractions to plasmin. Bovine euglobulin fractions contain an inhibitor which seems to be specifically directed towards urokinase and not to plasmin or to tissue plasminogen activator. Its inhibiting capacity is decreased after treatment with chloroform.

Animals↗
PubMed1985

Evaluation of euglobulin methods for the study of blood fibrinolytic activity: results for patients with rheumatoid arthritis and in the postoperative period.

Euglobulin fractionation is a frequently employed pretreatment of plasma for the determination of fibrinolytic activity. The fractionation procedure suffers from possible in vitro artifacts, e.g., variable precipitation of C1-inactivator. This is illustrated by the following two situations. It is shown that increased amounts of C1-inactivator not related to an increased plasma concentration are present in euglobulin fractions in cases of classic rheumatoid arthritis. Similarly, postoperatively, a disproportional increase in C1-inactivator in euglobulin fractions occurs. In both cases, an artificially reduced fibrinolytic activity is recorded due to increased inhibition by C1-inactivator. This is circumvented and recognized by adding sodium flufenamate or C1s-esterase to euglobulin fractions to uniformly eliminate C1-inactivator. Two specific assays for tissue-type plasminogen activator activity in euglobulin fractions (as C1-inactivator-resistant activator activity and a parabolic rate assay on a synthetic substrate) correlate excellently (r = 0.8728; p less than 0.001; n = 108). The first mentioned is corrected for variable endogenous C1-inactivator; the latter assay is found to be insensitive to inhibition by C1-inactivator. It is concluded that with euglobulin methods a misinterpretation of blood fibrinolytic activity is possible in rheumatoid arthritis patients. In the postoperative period, the fibrinolytic shutdown concerns tissue-type plasminogen activator activity; the pattern of the shutdown can be misjudged in using traditional euglobulin methods.

Abdomen↗
PubMed1991

Aspirin-sensitive asthma: significance of the cyclooxygenase-inhibiting and protein-binding properties of analgesic drugs.

The in vitro release of endogenous and exogenous PgF2 alpha from plasma and serum proteins by aspirin and other analgesic drugs has been studied by RIA and equilibrium-dialysis techniques, respectively. Before aspirin addition, the mean plasma level of PgF2 alpha measured by RIA was significantly lower in aspirin-sensitive asthma (ASA) patients (11.3 +/- 6.5 pg/ml; n = 8) than in aspirin-tolerant asthma (ATA) patients (25.0 +/- 11.4 pg/ml; n = 21). After aspirin addition (50 micrograms/ml) the mean PgF2 alpha level detected in plasma by RIA was higher in ASA patients (97.6 +/- 5.5 pg/ml) than in ATA patients (66.9 +/- 4.5). The binding of [3H]PgF2 alpha to serum protein was significantly inhibited by NSAIDs but not by paracetamol (0.2-1.0 mM). These results implicate PgF2 alpha and the protein-binding property of analgesic drugs in the pathogenesis of aspirin-sensitive asthma.

Acetaminophen↗
PubMed2001

The transient receptor potential protein homologue TRP6 is the essential component of vascular alpha(1)-adrenoceptor-activated Ca(2+)-permeable cation channel.

The Drosophila transient receptor potential protein (TRP) and its mammalian homologues are thought to be Ca(2+)-permeable cation channels activated by G protein (G(q/11))-coupled receptors and are regarded as an interesting molecular model for the Ca(2+) entry mechanisms associated with stimulated phosphoinositide turnover and store depletion. However, there is little unequivocal evidence linking mammalian TRPs with particular native functions. In this study, we have found that heterologous expression of murine TRP6 in HEK293 cells reproduces almost exactly the essential biophysical and pharmacological properties of alpha(1)-adrenoceptor-activated nonselective cation channels (alpha(1)-AR-NSCC) previously identified in rabbit portal vein smooth muscle. Such properties include activation by diacylglycerol; S-shaped current-voltage relationship; high divalent cation permeability; unitary conductance of 25 to 30 pS and augmentation by flufenamate and Ca(2+); and blockade by Cd(2+), La(3+), Gd(3+), SK&F96365, and amiloride. Reverse transcriptase-polymerase chain reaction and confocal laser scanning microscopy using TRP6-specific primers and antisera revealed that the level of TRP6 mRNA expression was remarkably high in both murine and rabbit portal vein smooth muscles as compared with other TRP subtypes, and the immunoreactivity to TRP6 protein was localized near the sarcolemmal region of single rabbit portal vein myocytes. Furthermore, treatment of primary cultured portal vein myocytes with TRP6 antisense oligonucleotides resulted in marked inhibition of TRP6 protein immunoreactivity as well as selective suppression of alpha(1)-adrenoceptor-activated, store depletion-independent cation current and Ba(2+) influx. These results strongly indicate that TRP6 is the essential component of the alpha(1)-AR-NSCC, which may serve as a store depletion-independent Ca(2+) entry pathway during increased sympathetic activity.

Adrenergic alpha-Agonists↗