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PubMed2006

Transcriptional regulation of metabotropic glutamate receptor 2/3 expression by the NF-kappaB pathway in primary dorsal root ganglia neurons: a possible mechanism for the analgesic effect of L-acetylcarnitine.

L-acetylcarnitine (LAC), a drug utilized for the treatment of neuropathic pain in humans, has been shown to induce analgesia in rodents by up-regulating the expression of metabotropic glutamate receptor 2 (mGlu2) in dorsal root ganglia (DRG). We now report that LAC-induced upregulation of mGlu2 expression in DRG cultures involves transcriptional activation mediated by nuclear factor-kappaB (NF-kappaB). A single application of LAC (250 muM) to DRG cultures induced a transient increase in mGlu2 mRNA, which was observable after 1 hour and was no longer detectable after 1 to 4 days. In contrast, LAC treatment had no effect on mGlu3 mRNA expression. Pharmacological inhibition of NF-kappaB binding to DNA by caffeic acid phenethyl ester (CAPE) (2.5 microg/ml for 30 minutes) reduced the constitutive expression of mGlu2 and mGlu3 mRNA after 1-4 days and reduced the constitutive expression of mGlu2/3 protein at 4 days. This evidence combined with the expression of p65/RelA and c-Rel in DRG neurons indicated that expression of mGlu2 and mGlu3 is endogenously regulated by the NF-kappaB family of transcription factors. Consistent with this idea, the transient increase in mGlu2 mRNA induced by LAC after 1 hour was completely suppressed by CAPE. Furthermore, LAC induced an increase in the acetylation of p65/RelA, a process that enhances the transcriptional activity of p65/RelA. These results are consistent with the hypothesis that LAC selectively induces the expression of mGlu2 by acting as a donor of acetyl groups, thus enhancing the activity of the NF-kappaB family of transcription factors. Accordingly, we show that carnitine, which has no effect on pain thresholds, had no effect on p65/RelA acetylation and did not enhance mGlu2 expression. Taken together, these results demonstrate that expression of mGlu2 and mGlu3 mRNA is regulated by the NF-kappaB transcriptional machinery, and that agents that increase acetylation and activation of NF-kappaB transcription factors might induce analgesia via upregulation of mGlu2 in DRG neurons.

Acetylcarnitine↗
PubMed1993

Inhibition of oxidative stress in HeLa cells by chemopreventive agents.

12-O-Tetradecanoylphorbol-13-acetate (TPA)-mediated oxidative stress in HeLa cells and its inhibition were studied by fluorometric measurement of H2O2 and by 3H-postlabeling of the oxidized bases 8-hydroxyl-2'-deoxyguanosine (8-OHdG) and 5-hydroxymethyl-2'-deoxyuridine (HMdU). TPA treatment (10 fmol/cell) caused approximately 7-fold increase in H2O2 levels (0.1 nmol TPA/ml), and 5-10-fold increase in 8-OHdG and HMdU (10 nmol TPA/ml). Naturally occurring compounds [caffeic acid phenethyl ester (CAPE), (-).epigallocatechin gallate (EGCG), penta-O-galloyl-beta-D-glucose (PGG) and sarcophytol A (Sarp A)] and the anticancer drug tamoxifen (TAM) were tested as potential chemopreventive agents. These agents dose-dependently inhibited TPA-induced H2O2, 8-OHdG and HMdU. The doses required for a 50% decrease in H2O2 were approximately 2.5 microM for TAM; 5 microM for CAPE, EGCG and PGG; and 75 microM for Sarp A. TAM and PGG (10 microM), EGCG (25 microM), and CAPE (50 microM) abolished TPA-mediated H2O2 production, even below the normal cellular levels. TAM (2.5-20 microM) decreased TPA-mediated HMdU and 8-OHdG formation 2-29 times. Maximum inhibition occurred at 20 microM TAM, which caused an approximately 95% decline in HMdU and 8-OHdG. CAPE was effective at 0.5-50 microM. CAPE (25 microM) decreased 8-OHdG 95%, and HMdU 58%, while Sarp A (250 microM) reduced 8-OHdG by 93% and HMdU by 78%. EGCG (1-25 microM) and PGG (1-10 microM) inhibited of 8-OHdG and HMdU dose-dependently. However, higher doses (50 and 100 microM) decreased the efficacy of that inhibition. Of those agents tested, TAM appears to be the most and Sarp A the least effective. Our results point to these 5 compounds as being potential chemopreventive agents, which at very low doses decrease the tumor promoter-mediated oxidative processes.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2002

Oxidative stress and inflammatory reaction modulation by white wine.

Wine and olive oil, essential components of the Mediterranean diet, are considered important factors for a healthy life style. Tyrosol (T) and caffeic acid (CA) are found in both extra virgin olive oil and in white wine. Three white wines from the northeast Italy and four white wines from Germany were analyzed for their content of T and CA. These compounds were tested for their antioxidant activity and their capacity to modulate three different cytokines: IL-1 beta, IL-6, and TNF-alpha, which are currently considered to be the major cytokines influencing the acute phase of the inflammatory response. Furthermore, the antioxidant activity of T and CA was analyzed by monitoring the oxidation of a redox-sensitive probe by using laser scanning confocal microscopy. T and CA, applied at nanomolar range, were found to significantly reduce the generation of oxidants induced by azobis-amidinopropanedihydrochloride. Peripheral blood mononuclear cells (PBMC) from healthy volunteers were incubated at 37 degrees C for 12 hours with 100 ng LPS (E. coli and P. maltofilia). Increasing doses of T and CA (150 nM to 300 microM) were added and cell-associated IL-1 beta and TNF-alpha were determined by immunoreactive tests after three freeze-thaw cycles. IL-6 release was also determined in cell surnatants. LPS-stimulated PBMC showed a significant increase in cytokine release, while T and CA, used at nanomolar concentrations, were able to modulate their expression. Taken together, these results suggest a remarkable effect of white wine non-alcoholic compounds on oxidative stress and inflammatory reaction.

Antioxidants↗
PubMed2004

Inhibition of tumor metastasis by sodium caffeate and its effect on angiogenesis.

OBJECTIVE: Sodium caffeate (SC), the sodium salt of caffeic acid, was synthesized in our laboratory. We studied the antimetastatic effect induced by SC and its inhibition of tumor angiogenesis using various in vitro and in vivo metastasis assays. METHODS: The in vivo inhibitory effect of SC on metastasis and angiogenesis was examined in the Lewis lung carcinoma pulmonary metastasis model and chicken chorioallantoic membrane (CAM) model, respectively. MTT assay and flow cytometry were used to measure the inhibition by SC of the proliferation of transformed human umbilical vein endothelial cells (ECV304) and the apoptosis induced by SC in ECV304 cells, respectively. A cell attachment assay was used to evaluate inhibition by SC of the adhesion activity of human high metastatic giant cell carcinoma of the lung (PG) cells. A cell invasion assay was used to evaluate the effect of SC on the ability of PG cells to cross tissue barriers. Inhibition by SC of gelatinase secretion in PG cells was determined by zymography. RESULTS: In vivo results showed that SC (1 g/kg i.p. for 14 days) inhibited pulmonary metastasis at a rate of 55%. There were no differences in animal weights among the groups. The angiogenesis of CAM was inhibited by SC (200 microg/egg) at a rate of 70%. In vitro studies showed that SC inhibited the proliferation of ECV304 cells by inducing apoptosis. SC also reduced the adhesion and invasion ability of PG cells and inhibited the secretion of MMP-2 and MMP-9 in PG cells. CONCLUSION: SC might be a potential antimetastatic agent with an antiangiogenic effect.

Angiogenesis Inhibitors↗
PubMed1995

Hydroxylated aromatic inhibitors of HIV-1 integrase.

Efficient replication of HIV-1 requires integration of a DNA copy of the viral genome into a chromosome of the host cell. Integration is catalyzed by the viral integrase, and we have previously reported that phenolic moieties in compounds such as flavones, caffeic acid phenethyl ester (CAPE, 2), and curcumin confer inhibitory activity against HIV-1 integrase. We now extend these findings by performing a comprehensive structure-activity relationship using CAPE analogues. Approximately 30 compounds have been prepared as HIV integrase inhibitors based on the structural lead provided by CAPE, which has previously been shown to exhibit an IC50 value of 7 microM in our integration assay. These analogues were designed to examine specific features of the parent CAPE structure which may be important for activity. Among the features examined for their effects on inhibitory potency were ring substitution, side chain length and composition, and phenyl ring conformational orientation. In an assay which measured the combined effect of two sequential steps, dinucleotide cleavage and strand transfer, several analogues have IC50 values for 3'-processing and strand transfer lower than those of CAPE. Inhibition of strand transfer was assayed using both blunt-ended and "precleaved" DNA substrates. Disintegration using an integrase mutant lacking the N-terminal zinc finger and C-terminal DNA-binding domains was also inhibited by these analogues, suggesting that the binding site for these compounds resides in the central catalytic core. Several CAPE analogues were also tested for selective activity against transformed cells. Taken together, these results suggest that the development of novel antiviral agents for the treatment of acquired immune deficiency syndrome can be based upon inhibition of HIV-1 integrase.

Animals↗
PubMed2005

Effects of CAPE-like compounds on HIV replication in vitro and modulation of cytokines in vivo.

OBJECTIVES: Five CAPE-like compounds, namely caffeic acid phenethyl ester (CAPE), methyl caffeate (MC), ethyl 3-(3,4-dihydroxyphenyl)acrylate (EC), phenethyl dimethyl caffeate (PEDMC) and phenethyl 3-(4-bromophenyl)acrylic (BrCAPE) were tested for their anti-HIV replication in vitro and immune modulation effects in vivo. METHODS: Short-term cytotoxicity was assessed by Trypan Blue stain and MTT assay. For antiviral assays, M-tropic (strain JRCSF), T-tropic (strain NL-4-3) and dual tropic (strain 89.6) HIV isolates were used in peripheral blood mononuclear cell (PBMC) culture. RESULTS: None of these CAPE-like compounds showed significant cytotoxicity in the treatment of PBMCs. By P24 EIA tests, CAPE, MC and EC significantly inhibited HIV replication in PBMC cells, but PEDMC and BrCAPE showed only slightly inhibitory effects. The in vivo modulatory effects on six cytokines [interleukin (IL)-2, IL-4, IL-6, interferon (IFN)-gamma, granulocyte-macrophage colony-stimulating factor (GM-CSF) and soluble Fas] were analysed. BALB/c mice treated with different doses or not treated with these CAPE-like chemicals showed that cytokines were increased to different extents by the different treatments. However, the concentrations of IL-6 and GM-CSF were not significantly affected by administration of any of these compounds (P > 0.05). CONCLUSIONS: The different effects of treatments on anti-HIV replication and cytokine modulation suggested that these compounds affect virological and immunological response via different mechanisms. The virological and immunological mechanisms and response to these treatments need to be elaborated in further studies in order to derive the structural features of more effective compounds. Since neither death nor pathological change in the mice were observed in this study, these CAPE-like compounds are worth studying further as potential chemotherapy agents for anti-HIV infection and cytokine modulation.

Animals↗
PubMed2005

Determination of hydrogen peroxide scavenging activity of cinnamic and benzoic acids employing a highly sensitive peroxyoxalate chemiluminescence-based assay: structure-activity relationships.

A series of cinnamic acids along with their corresponding benzoate analogues were tested for their ability to scavenge hydrogen peroxide (H(2)O(2)), by using a highly sensitive, peroxyoxalate chemiluminescence assay. Among benzoic acid derivatives, vanillic acid (3-hydroxy-4-methoxybenzoic acid) was found to be the most efficient H(2)O(2) scavenger with its hydrogen peroxide scavenging activity (SA(HP)) being 170.20 microM(-1), whereas protocatechuic acid (3,4-dihydroxybenzoic acid) exhibited the weakest activity (5.90 microM(-1)). Caffeic acid (3,4-dihydroxycinnamic acid) was the strongest antioxidant amongst cinnamate derivatives with a SA(HP) = 8.2 microM(-1), as opposed to m-coumaric acid (2-hydroxycinnamic acid), which was found to be a poor hydrogen peroxide scavenger (SA(HP) = 0.18 microM(-1)). Comparison between the two groups revealed that benzoate derivatives are much stronger hydrogen peroxide quenchers in relation with their cinnamate analogues, and this finding was discussed on a basis of structure-activity relationships and comparative assessment of other antioxidant characteristics.

Benzoates↗
PubMed2005

Protective effects of ellagic and chlorogenic acids against oxidative stress in PC12 cells.

Following exposure of differentiated neuronal PC12 cells to either t-BHP, hydrogen peroxide (H2O2) or FeSO4 various kinds of reactive oxygen species (ROS) are generated leading to oxidative injury. The protective effects of two plant polyphenols, ellagic (EC) and chlorogenic acid (CGA), as well as of two metabolites, caffeic acid (CA) and ferulic acid (FA), were investigated in preincubation and coincubation experiments with respect to the following parameters: prevention of cell death, GSH depletion, lipid peroxidation and ROS formation. The polyphenols more efficiently suppressed cytotoxicity and loss of GSH caused by peroxides than by iron, particularly in preincubation. Lipid peroxidation which increased much stronger in response to FeSO4 was counteracted completely by the polyphenols. In case of iron, however, only coincubation was effective. EA and CGA and the metabolites CA and FA showed excellent elimination of ROS induced by all stressors. These findings suggest that two dietary antioxidants, EA and CGA, may have protective properties against oxidative stress induced in CNS.

Animals↗
PubMed1994

Cellular pathways leading to melanoma differentiation: therapeutic implications.

The induction of differentiation, as evidenced by benign growth characteristics, dendritic morphology, pigmentation capability, and a mature antigenic phenotype, is an attractive theoretical basis for therapy in human melanoma. Melanoma differentiation can be experimentally induced by modulating intracellular pathways involving protein kinase C, tyrosine kinases, and protein kinase A, or by modulating nuclear transcription with retinoids, DNA-damaging agents, and chemotherapeutic drugs. Other experimental differentiating agents include the amino acid tyrosine, histamine receptor antagonists, polyamine antagonists, dimethylsulphoxide, caffeic acid ester, and butyrate. The mechanisms involved in the actions of many of these agents are beginning to be understood and the pathways are often intersecting; cross-talk in the form of negative and positive feedback loops is extensive. Uncoupling of pathways is also seen, with some agents leading to simultaneous increases in both differentiated and transformed characteristics. While clinical benefits of this approach have so far been sparse, greater understanding of the cellular pathways of differentiation may open new therapeutic options in melanoma.

Cell Transformation, Neoplastic↗
PubMed2003

Polyphenol pattern and antioxidant activity of different tomato lines and cultivars.

BACKGROUND/AIMS: Besides antioxidant vitamins and minerals, fruits and vegetables contain flavonoids and related phenolics. The biological activities of these polyphenols have become well known in recent years evidencing their beneficial effects on human health. In this context, the characterization of the flavonoids present in tomatoes is of great interest. Thus the polyphenol pattern (including flavonols, flavanones and cinnamate derivatives), lycopene and beta-carotene concentrations and the total antioxidant activity (TAA) of the phenolic fraction from different tomato lines and cultivars have been determined. METHODS: The characterization was obtained by means of spectrophotometry and HPLC analyses. RESULTS: Mean values for single flavonoids were 0.68 +/- 0.16 for naringenin, 0.74 +/- 0.12 for rutin and 0.32 +/- 0.06 for a rutin-pentoside. Mean total polyphenol content was 13.15 +/- 1.15 mg/100 g and mean TAA value was 1.3 +/- 0.10 mmol/g. The obtained TAA values resulted in good accordance with the total polyphenol content (R(2) = 0.7928). The main phenolic acids were chlorogenic (mean +/- SE 0.20 +/- 0.03) and caffeic acid (mean +/- SE 0.03 +/- 0.01). Mean levels of lycopene and beta-carotene were 5.38 +/- 0.90 and 1.18 +/- 0.40 mg/100 g, respectively. CONCLUSIONS: Almost all the lines characterised by low carotenoid content produce high levels of polyphenols, and consequently have the most powerful antioxidant potential.

Antioxidants↗
PubMed2005

Evaluation of polyphenolic acid esters as potential antioxidants.

Six polyphenolic acid esters were synthesized and their antioxidative properties were evaluated in three model systems [2,2'-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay, 2,2'-azobis(2-amidinopropane)dihydrochloride (AAPH)-induced lipid peroxidation system, and the dye-bleaching assay of peroxynitrite radical]. Among these compounds, we found that compounds 4 [3,4-dihydroxy-benzoic acid-(2-phenoxyethyl ester)], and 5 [3,4-dihydroxy-cinnamic acid-(2-phenoxyethyl ester)] provided comparable activity to caffeic acid phenethyl ester (CAPE) in the DPPH model. Compound 3 [2,5-dihydroxy-benzoic acid-(2-phenoxyethyl ester)], was found to be more active than CAPE in the AAPH system, it also displayed about 2-fold greater activity than CAPE in the peroxynitrite radical model. These results suggest that these phenolic acid ester derivatives, with their potent anti-oxidant activities, may have useful applications as antioxidants.

Antioxidants↗
PubMed1997

[Phenylarsine oxide, a tyrosine phosphatase inhibitor, induces an increase in the intracellular concentration of calcium in rat peritoneal macrophages and human fibroblasts].

Using Fura-2 microfluorimetry, phenylarsine oxide (PAO) (10-50 microM), a potent tyrosine phosphatase inhibitor, was shown to induce a dose-dependent increase in the free Ca2+ intracellular concentration in rat peritoneal macrophages and human foreskin fibroblasts. The PAO-induced increase in [Ca2+]i is not due presumably to depletion of intracellular Ca2+ stores but to mainly a stimulation of Ca2+ entry from the extracellular medium. This PAO-activated Ca2+ entry is attenuated by the following pharmacological agents. Organic and inorganic Ca2+ channel blockers: (nifedipine, verapamil and Ni2+); nonselective cation channel blocker niflumic acid; tyrosine kinase inhibitors genistein and methyl-2,5-dihydroxycinnamate; SH-reagents dithiothreitol parachloromercuribenzoate and N-ethylmaleimide; arachidonic acid metabolism inhibitors 4-bromophenacyl bromide, indomethacin and caffeic acid; microtubule disrupters vinblastine, colchicine and colcemide. On the contrary, microfilament disrupters, cytochalasin B and phalloidin, enhance PAO-activated Ca2+ entry. Our data suggest that the dynamic balance between tyrosine kinase and phosphatase activity may play a central role in the maintenance of homeostatic levels of [Ca2+]i both in unstimulated cells and after agonist application.

Animals↗
PubMed2001

Effect of ethyl esterification of phenolic acids on low-density lipoprotein oxidation.

Inhibition of copper-induced low-density lipoprotein (LDL) oxidation by phenolic acids and their ethyl esters was investigated. LDL oxidation was evaluated by the hydroperoxide concentration and the chromatographic pattern of apoprotein fractions after fast protein liquid chromatography (FPLC). Antiradical properties against 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical and 2,2'-azobis(2-amidinopropane)dihydrochloride (AAPH) were also investigated, and lipophilicity determined by thin-layer chromatography. Caffeic acid at 5 microM and sinapic acid at 10 microM protected LDL against oxidation, inhibiting both hydroperoxide formation and the increase of apoprotein negative charge. Ferulic, gallic and p-hydroxy cinnamic acids were ineffective. Ethyl esterification increased the lipophilicity of the five acids, and enhanced the antioxidant properties of caffeic, sinapic and ferulic acids. Ethyl caffeate was protective at 1 microM. In contrast, gallic and p-hydroxy cinnamic ethyl esters were ineffective. Our results indicate that ethyl esterification of phenolic acids increases lipophilicity of their ethyl esters and may enable a better incorporation into the lipid layer of the LDL particle and the exertion of their antioxidant effect in the true site of lipoperoxidation. However, increasing lipophilicity is not the only mechanism able to potentiate preexisting antioxidant properties of molecules, and probably other mechanisms are implicated.

Alkylation↗
PubMed1999

Phenolic composition of kiwifruit juice.

Phenolic compounds in kiwifruit pulp were separated and characterized by reversed-phase HPLC, and the effect of juice processing on the phenolic composition was studied. Fractionation of phenolic compounds was achieved through selective elution from C-18 cartridges prior to preconcentration and subsequent separation by HPLC. Strongly acidic compounds were identified as derivatives of coumaric and caffeic acids, including chlorogenic acid, protocatechuic acid, and a derivative of 3,4-dihydroxybenzoic acid. The weakly acidic fraction contained epicatechin, catechin, and procyanidins (B3, B2, or B4 and oligomers). Flavonols were present as the glycosides of quercetin (glucoside, rhamnoside, and rutinoside) and kaempferol (rhamnoside and rutinoside). Phenolic compounds were present, at levels of <1-7 mg/L, in clarified juice. The concentration of phenolics was highest after high-temperature short-time treatment (HTST) of juice. Hydrolysis of hydroxycinnamic acids occurred after enzyme addition and HTST treatment. The flavonol glycoside composition is the best identifier of kiwifruit juice.

Beverages↗
PubMed1985

Directional movement of cells in vivo and in vitro under the influence of 5-lipoxygenase inhibitors.

Five inhibitors of 5-lipoxygenase activity [phenidone, nordihydroguaiaretic acid (NDGA), BW755c, nafazatrom and the methyl ester of caffeic acid] have been compared with the cyclo-oxygenase inhibitor indomethacin as inhibitors of aggregation and chemotaxis by guinea-pig polymorphonuclear leukocytes. The results suggest that neither 5-lipoxygenase nor cyclo-oxygenase products are of significance in these in vitro assays. However, all of these compounds, with the exception of BW755c, significantly inhibited cell accumulation in an acute inflammatory model. These results cast doubt on the central importance of any individual arachidonic acid metabolite in the development of inflammation in vivo.

Animals↗
PubMed2004

Antioxidative activity of a zinc-chelating substance in coffee.

Coffee brew contains a brownish zinc-chelating polymer designated ApV. ApV was prepared from the precipitate formed in a solution of instant coffee by adding ZnCl(2) and purified using ion-exchange and cellulose column chromatographies. The antioxidative activities of ApV and related compounds were evaluated in this study. The free-radical scavenging activity of ApV estimated by ABTS assay was at a similar level to that of instant coffee, while the O(2)(-) scavenging activity of ApV, which is superoxide dismutase-like activity, was lower than that of instant coffee. The hydroxyl-radical scavenging activity of ApV was higher than that of instant coffee, and the auto-oxidation of linoleic acid was more strongly inhibited by ApV than by caffeic acid.

Absorption↗
PubMed2006

[Studies on chemical constituents of Paederia scandense].

OBJECTIVE: To study the chemical constituents of Paederia scandense. METHOD: The constituents were isolated and purified by silica gel and Sephadex LH - 20 column chromatography. Their structures were elucidated by physicochemical properties and spectral analysis. RESULT: 20 compounds were obtained and identified as rubiadin-1-methylether (1), diadzein (2), cleomiscosin B (3), cleomiscosin D (4), isolariciresinol (5), linarin (6), isoscopoletin (7), caffic acid (8), coumarinic acid (9), p-hydroxyl-benzoic acid (10), oleanolic acid (11), ursolic acid (12), beta-sitosterol (13), daucosterol (14), paederoside (15), paederosidic acid (16), paederosidic acid methyl ester (17), saprosmoside E (18), paederoscandoside (19), caffeic acid 4-O-beta-D-glucopyranoside (20). CONCLUSION: Compounds 1-10, and 20 were isolated from this plant for the first time.

Coumarins↗
PubMed1991

Arachidonic acid metabolites and chloride secretion in rabbit distal colonic mucosa.

The relationships between arachidonic acid (AA) metabolism and chloride secretion were investigated in mucosal preparations of rabbit distal colon. Tissues displayed a significant cyclooxygenase activity already in nonstimulated conditions and incubation with exogenous AA and calcium ionophore A23187 produced a predominant prostaglandin F2 alpha (PGF2 alpha) profile [PGF2 alpha greater than PGE2 greater than thromboxane B2 (TxB2) greater than 6-keto-PGF1 alpha] as assessed by HPLC of tissue homogenates, whereas 5-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE) was not detected in AA- or A23187-stimulated tissues. Radioimmunological assays showed that PGE2 synthesis was time dependent, plateaued at 10 min, and proceeded at rates 15-20 times over TxB2 and 6-keto-PGF1 alpha. Among the PGs produced by colonic mucosa, only PGE2 and, to a lower extent, PGF2 alpha were found to stimulate chloride secretion and cAMP synthesis. Pretreatment with 10 microM 5,8,11,14-eicosatetraynoic acid, a cyclo- and lipoxygenase inhibitor, prevented AA-induced chloride secretion and PG and cAMP synthesis with the same strength as the cyclooxygenase inhibitor indomethacin. No effects were found after preincubation with nordihydroguaiaretic acid, a lipoxygenase blocker with moderate cyclooxygenase inhibitory properties, and caffeic acid, a lipoxygenase inhibitor. 5-HETE (5 microM) had no effect on short-circuit currents (Isc) and chloride transport, but it significantly reduced the increase in Isc, chloride secretion, and PGE2 synthesis elicited by AA or A23187. Platelet-activating factor, reported to stimulate rabbit colon Isc through an indomethacin-sensitive pathway, was not detected at concentrations as low as 10(-10) M.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗