calcimycin has been researched along with azelastine* in 9 studies
9 other study(ies) available for calcimycin and azelastine
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Inhibition of leukotriene synthesis by azelastine.
Azelastine, oxatomide, and ketotifen are used for patients with allergic diseases. These drugs inhibit the release of chemical mediators including the leukotrienes; however, the mechanism involved is unclear.. To clarify the mechanism of inhibition, we investigated the effects of three drugs on the function of phospholipase A2, 5-lipoxygenase, leukotriene C4 synthase, and leukotriene A4 hydrolase, which are all catabolic enzymes involved in synthesizing leukotriene C4 and leukotriene B4 in rat basophilic leukemia (RBL)-1 cells.. The production of leukotriene C4 and leukotriene B4 was measured by high performance liquid chromatography (HPLC). All three drugs inhibited the production of leukotriene C4 and leukotriene B4 when cells were stimulated with A23187. All three drugs also inhibited the A23187-stimulated release of 3H-arachidonic acid from membrane phospholipids. Azelastine inhibited the production of leukotriene C4, but not leukotriene B4, when either arachidonic acid or leukotriene A4 free acid was used as the substrate in our cell free system. Oxatomide and ketotifen did not inhibit the synthesis of either leukotriene C4 or leukotriene B4 in the same cell free study.. Results indicated that oxatomide and ketotifen inhibit the production of leukotriene C4 and leukotriene B4 by inhibiting phospholipase A2 activity, whereas, azelastine inhibits the leukotriene C4 production by inhibiting phospholipase A2 and leukotriene C4 synthase. Topics: Animals; Anti-Allergic Agents; Calcimycin; Epoxide Hydrolases; Glutathione Transferase; Leukemia, Basophilic, Acute; Leukotriene B4; Leukotriene C4; Lipoxygenase Inhibitors; Phospholipases A; Phospholipases A2; Phthalazines; Rats; Tumor Cells, Cultured | 1996 |
Inhibitory effects of azelastine and tranilast on leukotriene B4 and leukotriene C4 generation by rat colonic mucosa.
Anti-allergic drugs such as sodium cromoglycate are known to be effective for the treatment of ulcerative colitis (UC). Because leukotriene (LT) production is considered to play an important role in the pathophysiology of UC, we examined the effect of the anti-allergic drugs, azelastine and tranilast, and the 5-lipoxygenase inhibitor, AA861, on LTB4 and LTC4 production by isolated rat colonic mucosa treated with the calcium ionophore, A23187. Preincubation of colonic mucosa with AA861 (10(-4) M) or azelastine (10(-4) M) significantly reduced AA23187-induced LTB4 (p < 0.01 and p < 0.05, respectively) and LTC4 (p < 0.01) production. Pretreatment with tranilast (10(-3) M) also significantly reduced A23187-induced LTC4 production (p < 0.05). These findings suggest that azelastine and tranilast can inhibit LT production in colonic mucosa and may be beneficial in the treatment of patients with UC. Topics: Animals; Anti-Allergic Agents; Calcimycin; Colon; Intestinal Mucosa; Leukotriene B4; Leukotriene C4; Male; ortho-Aminobenzoates; Phthalazines; Rats; Rats, Wistar | 1995 |
Inhibitory effects of azelastine hydrochloride on Ca2+ influx, actin polymerization and release of eosinophil cationic protein of an eosinophilic leukaemia cell line EoL-1.
The inhibitory effects of azelastine hydrochloride on PAF-induced and fMLP-induced Ca2+ influx, actin polymerization and calcium ionophore A23187-induced and aggregated IgG-induced release of eosinophil cationic protein (ECP) of an eosinophilic leukaemia cell line, EoL-1, were examined. EoL-1 cells cultured with 0.2 mM dibutyryladenosine-cyclic monophosphate for 48 hours showed an increase in intracellular free Ca2+ concentration ([Ca2+]i) and actin polymerization when stimulated by PAF and fMLP. Azelastine hydrochloride inhibited PAF-induced and fMLP-induced Ca2+ influx ([Ca2+]i) in a dose-dependent manner with an IC50 of 1 x 10(-8) M and 1 x 10(-7) M, respectively. It also inhibited PAF-induced and fMLP-induced actin polymerization in a dose-dependent manner up to 40% and 30%, respectively. EoL-1 cells were differentiated to contain ECP in their eosinophilic granules when cultured for 9 days with supernatants of a human adult T cell leukaemia cell line, HIL-3 (HIL-3 sup). Calcium ionophore A23187 and aggregated IgG induced the secretion of ECP by EoL-1 cells. Azelastine hydrochloride inhibited the secretion of ECP in a dose-dependent manner. These inhibitory effects were seen even at therapeutic concentrations of 10(-8) M to 10(-9) M. These results indicate that the therapeutic effects of azelastine hydrochloride as an anti-allergic agent may include inhibition of the accumulation of eosinophils into the locus of allergic inflammation and of the release of cytotoxic granules from eosinophils. Topics: Actins; Blood Proteins; Bucladesine; Calcimycin; Calcium-Transporting ATPases; Cell Differentiation; Culture Media; Dose-Response Relationship, Drug; Eosinophil Granule Proteins; Eosinophils; Humans; Hypersensitivity; Immunoglobulin G; Inflammation; Leukemia, Eosinophilic, Acute; Leukemia, T-Cell; Lipoxygenase Inhibitors; N-Formylmethionine Leucyl-Phenylalanine; Phthalazines; Platelet Activating Factor; Polymers; Ribonucleases; Tumor Cells, Cultured | 1993 |
Inhibition of 5-HETE, LTB4, and LTC4 formation by azelastine in rat mixed peritoneal cells.
Azelastine produced a concentration-dependent inhibition of calcium ionophore A23187 (0.2 microM) stimulated generation of 5-HETE, leukotriene B4, and leukotriene C4 in rat mixed peritoneal cells, yielding IC50 values of 35.5, 47.4, and 31.7 microM, respectively. Nordihydroguaiaretic acid (a potent 5-lipoxygenase inhibitor) also exerted a strong and concentration-dependent inhibition of 5-HETE and leukotriene B4 and C4 formation with IC50 values of 0.15, 0.09, and 0.1 microM, respectively. The inhibition of the formation of the products of the lipoxygenase pathway of arachidonic acid metabolism by azelastine may contribute to its overall antiallergic, antiasthmatic, and pulmonary anti-inflammatory activities. Topics: Animals; Calcimycin; Depression, Chemical; Histamine H1 Antagonists; Hydroxyeicosatetraenoic Acids; Leukotriene B4; Peritoneal Cavity; Phthalazines; Radioimmunoassay; Rats; SRS-A | 1990 |
Azelastine inhibits stimulated histamine release from human lung tissue in vitro but does not alter cyclic nucleotide content.
To investigate the mechanism by which azelastine may be effective therapeutically in asthma, we studied its ability to inhibit anti-IgE- and calcium ionophore A23187-stimulated histamine release from human lung and to alter lung cyclic nucleotide levels. Significant inhibition of histamine release from both anti-IgE- and A23187-stimulated human tissue was apparent after 30 minutes preincubation of the lung tissue in azelastine. Significant inhibition of anti-IgE-stimulated histamine release was consistently seen in azelastine concentrations greater than or equal to 5 microM, and was dose dependent (r = 0.71, p less than 0.05) with maximal mean inhibition of 53 +/- 11%. For A23187-stimulated lung tissue, consistent inhibition of histamine release was not found until we used 30 microM azelastine, mean 35 +/- 11%. Inhibition in azelastine concentrations below 30 microM was variable and not significant. Lung cyclic AMP and cyclic GMP content was not significantly altered by incubation of lung tissue in 100 microM azelastine. We conclude that azelastine inhibits stimulated histamine release from human lung tissue in vitro but does not alter cyclic nucleotide content. Topics: Antibodies, Anti-Idiotypic; Calcimycin; Cyclic AMP; Cyclic GMP; Histamine H1 Antagonists; Histamine Release; Humans; Immunoglobulin E; Lung; Phthalazines; Pyridazines | 1989 |
Effect of azelastine on leukotriene synthesis in murine peritoneal cells and on thromboxane synthesis in human platelets.
Azelastine, a newly synthesized antiallergic agent, strikingly inhibited the production of leukotriene B4 and C4 (LTB4 and LTC4) in murine peritoneal cells which had been stimulated by calcium ionophore A23187. The 50% inhibitory concentrations (IC50) of the agent were approximately 1.0 x 10(-5) M. In addition, azelastine significantly inhibited also 5-lipoxygenase activity in peritoneal cells with an IC50 of 1.0 x 10(-5) M, but not on LTC4 synthetase, LTA4 hydrolase or phospholipase A2 activity. Furthermore, azelastine showed little effect on either 12-lipoxygenase activity or thromboxane synthesis in human platelets. These results suggest that at least the drug's antiallergic effects can be attributed to its inhibiting action of 5-lipoxygenase in regard to arachidonate metabolism. Topics: Animals; Blood Platelets; Calcimycin; Dose-Response Relationship, Drug; Epoxide Hydrolases; Glutathione Transferase; Hydroxyeicosatetraenoic Acids; Ketotifen; Leukotrienes; Lipoxygenase; Mice; ortho-Aminobenzoates; Peritoneal Cavity; Phospholipases A; Phospholipases A2; Phthalazines; Piperazines; Pyridazines; Thromboxanes | 1989 |
The effect of azelastine on neutrophil and eosinophil generation of superoxide.
Azelastine is a new investigational drug used to treat rhinitis and asthma. In addition to described actions that include inhibition of immunologic release of histamine from mast cells and basophils, blockade of smooth muscle contraction to various spasmogenic mediators, and relaxation of airway smooth muscle, azelastine has been ascribed anti-inflammatory properties. To understand further the mechanisms by which azelastine may regulate inflammation, its effect on neutrophil and eosinophil superoxide (O2-) generation was evaluated. Purified suspension of neutrophils (greater than 95% pure) and eosinophils (greater than 85% pure) were isolated from human peripheral blood samples by continuous density gradients of Percoll. The isolated granulocyte suspensions (1 x 10(5) cells) were added to 96-well microtiter plates in the presence of cytochrome c, activated by either N-formyl-methionyl-leucyl-phenylalanine, phorbol myristate acetate, calcium ionophore A23187, or opsonized zymosan particles; O2- generation was measured by the reduction of cytochrome c. We found that azelastine significantly inhibited both neutrophil and eosinophil generation of O2- in a dose-dependent fashion (10(-7) to 10(-5) mol/L) with each activator except zymosan. Furthermore, the degree to which azelastine suppressed O2- was similar in neutrophils and eosinophils. Thus, azelastine, in concentrations achieved therapeutically, inhibited granulocyte generation of O2-. This anti-inflammatory effect may also be beneficial in the treatment of asthma. Topics: Adult; Calcimycin; Eosinophils; Free Radicals; Histamine H1 Antagonists; Humans; N-Formylmethionine Leucyl-Phenylalanine; Phthalazines; Protein Kinase C; Pyridazines; Superoxides; Tetradecanoylphorbol Acetate; Zymosan | 1989 |
Effects of various drugs on superoxide generation, arachidonic acid release and phospholipase A2 in polymorphonuclear leukocytes.
The effects of variety of drugs on metabolic burst and phospholipase A2 in polymorphonuclear leukocytes (PMNs) were investigated. The stimulation of PMNs by n-formyl-methionyl-leucyl-phenylalanine (FMLP) causes arachidonic acid (AA) to be released in the cells concomitantly with the generation of superoxide anion. These variables were effectively diminished with some clinically employed drugs including chlorpromazine, trifluoperazine, azelastine, clemastine and mepacrine at the lower concentration of 20 microM. In contrast, indomethacin and procaine were ineffective even at the higher concentration of 100 microM. Subcellular fractionation of PMNs revealed that phospholipase A2 activity was located both in the plasma membrane-rich fraction as well as the granule-microsome-rich fraction, and the potency of inhibition of membrane-bound phospholipase A2 by the above mentioned drugs was: indomethacin (IC50 = 3 microM) less than chlorpromazine less than azelastine and clemastine (IC50 greater than 100 microM). The low potency of antipsychotropic drugs and antihistaminic drugs in inhibiting the fractionated phospholipase A2 contrast with the high efficiency with which they inhibit the superoxide generation and the AA release from stimulated PMNs. The AA releases from the PMNs stimulated by FMLP or calcium ionophore (A23187) were almost equally diminished by various drugs at the lower concentration. From these observations, it appeared likely that these drugs might inhibit the metabolic stimulations of PMNs at the sites of the Ca2+-dependent activation processes of the enzymes responsible for the AA release and the superoxide generation. Topics: Animals; Arachidonic Acid; Arachidonic Acids; Calcimycin; Chlorpromazine; Histamine H1 Antagonists; In Vitro Techniques; Indomethacin; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Phospholipases; Phospholipases A; Phospholipases A2; Phthalazines; Rabbits; Superoxides | 1988 |
Inhibition of calcium ionophore (A23187)-stimulated histamine release from rat peritoneal mast cells by azelastine: implications for its mode of action.
Azelastine is a novel, orally effective, long-acting, antiallergic agent. The ability of azelastine to influence calcium ionophore A23187-induced histamine release from rat peritoneal mast cells was investigated and compared with selected antiallergic drugs. The concentrations of drugs required to inhibit A23187 (0.2 microM)-stimulated histamine release by 50% (IC50S, microM) were as follows: azelastine 5; diphenhydramine 52; and ketotifen 200. Theophylline and sodium cromoglycate in a concentration range of 0.1-1000 microM failed to exert any significant inhibition of histamine release. The inhibitory effects of azelastine on A23187-stimulated histamine release were antagonized by high concentrations of exogenous Ca2+ ions. These data suggest that azelastine inhibits A23187-stimulated histamine release by interfering with the influx of Ca2+ into the mast cells. Topics: Animals; Ascitic Fluid; Calcimycin; Calcium; Diphenhydramine; Histamine H1 Antagonists; Histamine Release; Ketotifen; Male; Mast Cells; Phthalazines; Pyridazines; Rats; Rats, Inbred Strains | 1983 |