Differential inhibitory effects of vitamin E and other antioxidants on prostaglandin synthetase, platelet aggregation and lipoxidase

Panganamala, R.V.; Miller, James S.; Gwebu, Ephraim T.; Sharma, Hari; Cornwell, David G.

doi:10.1016/0090-6980(77)90171-x

Cited by 126 publications

(31 citation statements)

References 17 publications

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“…To further substantiate this suggestion, three additional inhibitors of the lipoxygenase enzyme system (NDGA, vitamin E, and a-naphthol; (21) were studied. All three antioxidants inhibited mucous release, NDGA did so in a dose-related fashion.…”

Section: Resultsmentioning

confidence: 99%

Effects of Arachidonic Acid, Monohydroxyeicosatetraenoic Acid and Prostaglandins on the Release of Mucous Glycoproteins from Human Airways In Vitro

Marom¹,

Shelhamer²,

Kaliner³

1981

J. Clin. Invest.

233

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A B S T R A C T (eicosa-5,8, 11,14-tetraynoic acid; vitamin E; nordihydroguaiaretic acid; and a-naphthol) inhibit mucous release. Three additional lines of evidence directly indicate that miionohydroxyeicosatetraenoic acid (HETE) causes increased mucous release: (a) the addition of a mixture of synthetic HETE (24-600 nM) increases mucous release; (b) pure 12-HETE (1-100 nM) also increases mucous release; (c) mucous release is increased synergistically by the combination of HETE and NSIAD.

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Section: Resultsmentioning

confidence: 99%

Effects of Arachidonic Acid, Monohydroxyeicosatetraenoic Acid and Prostaglandins on the Release of Mucous Glycoproteins from Human Airways In Vitro

Marom¹,

Shelhamer²,

Kaliner³

1981

J. Clin. Invest.

233

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“…We therefore examined the effect of the lipoxygenase inhibitor NDGA (29). In both rabbit colon and guinea pig ileum NDGA inhibited the response to BK (Figs.…”

Section: Methodsmentioning

confidence: 99%

Bradykinin-stimulated electrolyte secretion in rabbit and guinea pig intestine. Involvement of arachidonic acid metabolites.

Musch¹,

Kachur²,

Miller³

et al. 1983

J. Clin. Invest.

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A B S T R A C T Bradykinin (BK) increases short-circuit current (Isc) when added to the serosal side of rabbit or guinea pig ileum or rabbit colon. Significant effects on Isc are seen at concentrations as low as 10-' M. Anion substitution experiments and unidirectional 36C flux measurements indicate that this effect of BK on Isc is due to Cl secretion. The effect of BK on Isc can be partially blocked (60-70% inhibition) by cyclooxygenase inhibitors (indomethacin and/or naproxen) and completely blocked by the phospholipase inhibitor, mepacrine. The combined cyclooxygenase/lipoxygenase inhibitors BW 755 and eicosa-5,8,11,14-tetraynoic acid (ETYA) also completely block the effect of BK on Isc but the slow-reacting substance of anaphylaxis (SRS-A) antagonist FPL 55712 has no effect. None 5 January 1983. this effect can be blocked by prior addition of either indomethacin or mepacrine. These effects of BK are similar to those of exogenously added arachidonic acid (AA). AA also stimulates Cl secretion and increases PGE2 synthesis and its effect on Isc can be inhibited by prior desensitization to PGE2 or by prior addition of indomethacin. The above results indicate that BK stimulates active Cl secretion in both small and large intestine and suggest that this effect is due to the intracellular release of AA. Although the prostaglandins appear to be the major products of AA metabolism contributing to the secretory response, lipoxygenase products may also play a role.

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“…Inhibitors of cytochrome P-450, piperonyl butoxide, and SKF 525A, compounds of dissimilar structure, blocked the stimulated ACTH release at relatively low concentrations in a dose-dependent manner. Lipoxygenase and epoxygenase inhibitors reduced ACTH release at concentrations similar to those reported to inhibit the lipoxygenase and the cytochrome P-450 epoxygenase enzymes, respectively (18)(19)(20)(21)(22)(23). The epoxygenase can also be effectively blocked by the three lipoxygenase inhibitors used in this study (22,23).…”

Section: Discussionmentioning

confidence: 58%

“…2). The lipoxygenase inhibitors nordihydroguaieretic acid and butylated hydroxytoluene (18)(19)(20) suppressed the receptor-mediated ACTH secretion (Fig. 2).…”

Section: Resultsmentioning

confidence: 99%

Inhibitors of the cytochrome P-450 enzymes block the secretagogue-induced release of corticotropin in mouse pituitary tumor cells.

Luini

Axelrod

1985

Proc. Natl. Acad. Sci. U.S.A.

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A mouse pituitary tumor cell line (AtT-20) releases corticotropin (ACTH) in response to a number of secretagogues, iWciuding corticotropin-releasing factor (CRF), j3-adrenergic aints, N6,02'-dibutyryladenosine 3',5'-cyclic monophosphate (Bt2 cAMP), and potassium. The AtT-20 mouse pituitary cell line is a well-characterized model system to study corticotropin (ACTH) secretion. These cells release ACTH in response to a number of secretagogues, including corticotropin-releasing factor (CRF), isoproterenol, vasoactive intestinal peptide, the Ca2+ ionophore A23187, and potassium (1). It has been shown that the second messengers cAMP and Ca2+ (1), as well as phospholipid methylation (2), are involved in the mediation of these secretory responses. There has also been indirect evidence suggesting that arachidonic acid and/or its metabolites may be involved in ACTH secretion in AtT-20 cells. Phorbol esters and melittin, activators of phospholipase A2 (3-7), the enzyme that liberates arachidonic acid from lipids, are potent stimulators of ACTH secretion (8, 9). The synthetic corticosterone dexamethasone, which exerts some of its actions by inhibiting phospholipase A2 (10), blocks ACTH release (1). These findings prompted an investigation as to whether arachidonic acid or one or more of its many metabolites are involved in receptor-mediated ACTH secretion.Arachidonic acid is metabolized via three pathways: cycloxygenase, which generates prostaglandins and tromboxanes, lipoxygenase, which forms leukotrienes, and the NADPH-dependent cytochrome P-450 enzymes (epoxygenase), which forms epoxide metabolites (11). To ascertain whether metabolites of these pathways are involved in ACTH release, inhibitors of each of these enzymes as well as phospholipase A2 were used. We find that inhibitors of phospholipase A2, lipoxygenase, and epoxygenase, but not cycloxygenase, block the release of ACTH in AtT-20 cells. MATERIALS AND METHODSSynthetic CRF was obtained from Bachem Fine Chemicals (Torrance, CA), (-)-isoproterenol (+)-bitartrate, human serum albumin, 3-isobutyl-1-methylx4thine (IBMX), melittin, phorbol myristate acetate, nordihydrbguaieretic acid, butylated hydroxytoluene, p-bromophenacyl-bromide, mepacrine, A23187, N6,02'-dibutyryladenosine 3',5'-cyclic monophosphate (Bt2cAMP), 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP), and barbital were from Sigma. Forskolin was purchased from Calbiochem-Behring. Icosatetraynoic acid was kindly supplied by F. Hirata. Piperonyl butoxide and 2-diethylaminoethyl-2,2-diphenylvalerate (SKF 525A) were a generous gift from J. Gillette.Cell Culture Methods. AtT-20/D16-16 cells were grown and subcultured in Dulbecco's modified Eagle's medium (DME medium) with 10% calf serum, as described (12). Cells were plated in 30-mm (diameter) culture dishes at an initial density of 1.5 x 105 cells per well and were used 5-6 days after plating (60-80% confluency). For ACTH secretion studies, cells were equilibrated for 30 min at 37°C in 1 ml of DME medium/25 mM Hepes, pH 7.4, containing bovine s...

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Differential inhibitory effects of vitamin E and other antioxidants on prostaglandin synthetase, platelet aggregation and lipoxidase

Cited by 126 publications

References 17 publications

Effects of Arachidonic Acid, Monohydroxyeicosatetraenoic Acid and Prostaglandins on the Release of Mucous Glycoproteins from Human Airways In Vitro

Effects of Arachidonic Acid, Monohydroxyeicosatetraenoic Acid and Prostaglandins on the Release of Mucous Glycoproteins from Human Airways In Vitro

Bradykinin-stimulated electrolyte secretion in rabbit and guinea pig intestine. Involvement of arachidonic acid metabolites.

Inhibitors of the cytochrome P-450 enzymes block the secretagogue-induced release of corticotropin in mouse pituitary tumor cells.

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