Anti-inflammatory and platelet anti-aggregant activity of phospholipase-A2 inhibitors

Vallee, E.; Gougat, J; Jl, Navarro; Delahayes, J F

doi:10.1111/j.2042-7158.1979.tb13597.x

Cited by 69 publications

(22 citation statements)

References 19 publications

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“…On the other hand, PGE2 failed to overcome the inhibitory effect of BPB, a phospholipase A2 inhibitor (22). In addition, the inhibitory effect of BPB was partially but significantly overcome by arachidonic acid.…”

Section: Resultsmentioning

confidence: 88%

Inhibition of Teleocidin-Caused Epidermal Ornithine Decarboxylase Induction by Phospholipase A2-, Cyclooxygenase- and Lipoxygenase-lnhibitors

Nakadate

Aizu

Yamamoto

et al. 1985

Japanese Journal of Pharmacology

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Section: Resultsmentioning

confidence: 88%

Inhibition of Teleocidin-Caused Epidermal Ornithine Decarboxylase Induction by Phospholipase A2-, Cyclooxygenase- and Lipoxygenase-lnhibitors

Nakadate

Aizu

Yamamoto

et al. 1985

Japanese Journal of Pharmacology

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“…Removal of the endothelium abolished the increased cGMP levels and the relaxations to ATP, thrombin, and trypsin. These agents presumably activate phospholipase A 2 , since bromophenacyl bromide, a phospholipase A 2 inhib-itor (Roberts et al, 1977;Vallee et al, 1979;Thakkar et al, 1983), inhibited increased cGMP levels and relaxation induced by ATP and thrombin, whereas increased levels of cGMP and relaxation caused by sodium nitroprusside, an endothelium-independent relaxant Murad, 1983a, 1983b), were unaltered. Bromophenacyl bromide has also been shown to inhibit endothelium-independent relaxation to acetylcholine and Ca ++ ionophore A23187 in rabbit aorta and canine arteries (Furchgott et al, 1982).…”

Section: Discussionmentioning

confidence: 99%

“…Indomethadn, a cyclooxygenase inhibitor (Flower, 1974), potentiated the endothelium-dependent relaxations (Table 1), as well as the relaxations to sodium nitroprusside and isoproterenol (data not shown). Bromophenacyl bromide, an inhibitor of phospholipase (Roberts et al, 1977;Vallee et al, 1979;Thakker et al, 1983), inhibited the endothelium-dependent relaxations. The contractile responses to 0.1 HM norepinephrine after pretreatment with 0.1 mM ETYA, 10 fiM nordihydroguaiaretic add, and 0.1 mM indomethadn were significantly reduced to 71.2 ± 3.6, 46.4 ± 3.0, and 53.7 ± 4.2% (mean ± SE) of control, respectively, while the responses to norepinephrine following .3 fiM bromophenacyl bromide pretreatment were 94.8 ± 13.9% (mean ± SE) of control.…”

Section: Effect Of Agents and Removal Of The Endothelium On Atp- Thrmentioning

confidence: 99%

Mechanisms of adenosine triphosphate-, thrombin-, and trypsin-induced relaxation of rat thoracic aorta.

Rapoport¹,

Draznin²,

Murad³

1984

Circulation Research

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SUMMARY. The mechanisms by which adenosine triphosphate, thrombin, and trypsin cause relaxation of vascular smooth muscle were investigated. Relaxation of the rat thoracic aorta with adenosine triphosphate, thrombin, and/or trypsin was associated with increased levels of cyclic guanosine monophosphate in both time-and concentration-dependent manners. Thrombin and trypsin did not alter cyclic adenosine monophosphate levels, whereas adenosine triphosphate increased cyclic adenosine monophosphate levels after significant relaxation occurred. Removal of the endothelium abolished adenosine triphosphate-, thrombin-, and trypsin-induced relaxation and the associated increased levels of cyclic nucleotides. Relaxation due to these agents was also inhibited by exposure to nordihydroguaiaretic acid, a lipoxygenase inhibitor, and eicosatetraynoic acid, a lipoxygenase and cyclooxygenase inhibitor. Indomethacin, a cyclooxygenase inhibitor, potentiated relaxation to these agents, whereas the increased levels of cyclic nucleotides due to adenosine triphosphate were unaltered. Bromophenacyl bromide, a phospholipase A 2 inhibitor, decreased relaxation due to adenosine triphosphate, thrombin, and trypsin and the associated increased levels of cyclic nucleotides. Removal of extracellular calcium, which also presumably inhibits phospholipase A2, prevented the elevated levels of cyclic nucleotides and the inhibitory effects of adenosine triphosphate and trypsin on contraction. In contrast, sodium nitroprussideinduced relaxation and/or increased levels of cyclic guanosine monophosphate were unaltered by nordihydroguaiaretic acid, eicosatetraynoic acid, bromophenacyl bromide, and removal of extracellular calcium. After incubation of intact tissue with 32 P-orthophosphate, the patterns of protein phosphorylation caused by adenosine triphosphate, thrombin, and trypsin were indistinguishable from those of acetylcholine, sodium nitroprusside and 8-bromo cyclic guanosine monophosphate. All these agents dephosphorylated myosin light chain. Thus, the present study supports the hypothesis that relaxation induced by adenosine triphosphate, thrombin, and trypsin is mediated through the formation of an endothelial factor which elevates cyclic guanosine monophosphate levels and causes cyclic guanosine monophosphate-dependent protein phosphorylation and dephosphorylation of myosin light chain. (Circ Res 55: 468-479, 1984) ENDOTHELIUM-dependent vasodilation induced by acetylcholine, histamine and Ca ++ ionophore A23187 has recently been shown to be associated with the formation of cyclic guanosine monophosphate (cGMP) in both a time-and concentrationdependent manner in rat thoracic aorta . Furthermore, an inhibitor of phospholipase A 2 , quinacrine, and an inhibitor of lipoxygenase and cyclooxygenase, eicosatetraynoic acid (ETYA), inhibited acetylcholine-induced relaxation and the formation of cGMP . These results confirmed those of others (Furchgott and Zawadzki, 1980a;Furchgott et al., 1981;Furchgott, 1983) which suggested that relaxation cause...

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“…Both mepacrine and p-bromophenacyl bromide completely blocked the contraction. Both agents have been used as inhibitors of phospholipase A2 (Vargaftig & Dao Hai, 1972;Volwerk et al, 1974;Flower & Blackwell, 1976;Vallee et al, 1979;Yamamoto et al, 1982) to prevent liberation of arachidonic acid with subsequent production of its active metabolites. However, GUII-induced contractions were unaffected by cyclo-oxygenase (indomethacin) or lipoxygenase (nordihydroguaiaretic acid) inhibitors suggesting that products of arachidonate metabolism utilising these enzymes were not involved.…”

Section: Discussionmentioning

confidence: 99%

Complex effects of Gillichthys urotensin II on rat aortic strips

Gibson

1987

British J Pharmacology

103

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6LX1 The aim of this study was to determine whether the fish neuropeptide, Gillichthys urotensin II (GUII), possesses significant biological activity on rat aortic strips. 2 On intact strips, pre-contracted by noradrenaline (100 nM), low concentrations (0.1-0.5 nM) of GUII produced relaxations, while higher concentrations (1-10 nM) caused further contraction. On strips rubbed to remove endothelial cells, relaxations were absent but contractile responses to higher concentrations of GUII remained. 3 GUII (0.2-10nM) produced dose-related contractions of quiescent, intact aortic strips. These contractions consisted of two components, tonic and phasic, and were potentiated in rubbed strips and in the presence of the antioxidant drug hydroquinone (1O iM).4 Mepacrine (40 jM) and p-bromophenacyl bromide (50 gM) completely abolished contractions to GUII, but indomethacin (10 jM) and nordihydro-guaiaretic acid (1I0 M) were without effect. 5 The phasic, but not the tonic, component of the contractile response was inhibited by nitrendipine (200 nM), and was absent in bathing medium from which Ca2' had been omitted. Addition of EGTA (2 mM) to Ca2+-free bathing medium abolished the residual tonic component. 6 GUII-induced contractions were completely abolished by the calmodulin antagonists trifluoperazine (50 pM) and W-7 (30 gM).7 It is concluded that GUII, previously considered devoid of significant activity on mammalian tissues, produces potent endothelium-dependent relaxations and endothelium-independent contractions of rat aorta, and possible mechanisms underlying each response are discussed.

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Anti-inflammatory and platelet anti-aggregant activity of phospholipase-A2 inhibitors

Cited by 69 publications

References 19 publications

Inhibition of Teleocidin-Caused Epidermal Ornithine Decarboxylase Induction by Phospholipase A2-, Cyclooxygenase- and Lipoxygenase-lnhibitors

Inhibition of Teleocidin-Caused Epidermal Ornithine Decarboxylase Induction by Phospholipase A2-, Cyclooxygenase- and Lipoxygenase-lnhibitors

Mechanisms of adenosine triphosphate-, thrombin-, and trypsin-induced relaxation of rat thoracic aorta.

Complex effects of Gillichthys urotensin II on rat aortic strips

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