Arachidonate lipoxygenase inhibitors in guinea-pig isolated trachea. Effects on contractions to antigen and various agonists

Yamamoto, Akira; Shikada, Ken-ichi; Tanaka, Sakuya

doi:10.1016/0090-6980(90)90006-h

Cited by 5 publications

(4 citation statements)

References 14 publications

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“…Melittin caused a contraction that was slow in onset of the tracheal strip isolated from a guinea-pig in the presence of the cyclo-oxygenase inhibitor, indomethacin. Our previous study showed that the melittin-induced contractile response was significantly inhibited by both the peptide-leukotriene receptor antagonist, FPL55712, and the lipoxygenase inhibitor, nordihydroguaiaretic acid; similar results were obtained for AA-induced contraction (Yamamoto et al, 1990). We therefore suggested that melittin could contract the guineapig isolated trachea by promoting the formation of AA lipoxygenase products.…”

Section: Discussionsupporting

confidence: 64%

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Influence of epithelium on the inhibition of melittin‐induced contraction of guinea‐pig isolated trachea by the potassium channel opener NIP‐121

Shikada

Tanaka

1993

British J Pharmacology

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We have investigated the effect of the potassium channel opener, NIP‐121, on contraction elicited by melittin (a phospholipase A2 activator) in epithelium‐intact and epithelium‐denuded trachea isolated from guinea‐pigs. The effects of NIP‐121 were compared with those of isoprenaline, aminophylline and hydrocortisone. In the presence of the cyclo‐oxygenase inhibitor, indomethacin (5 μm), melittin (3 μg ml−1) caused time‐dependent contraction. The melittin‐induced contractile response was significantly augmented by removal of the epithelium and was concentration‐dependently and completely inhibited by the phospholipase A2 (PLA2) inhibitor, p‐bromophenacyl bromide (BPB 10–100 μm), and the lipoxygenase inhibitor, phenidone (10–300 μm). Similar inhibition of the melittin response by BPB (10 μm) and phenidone (10 μm) was observed in the epithelium‐denuded trachea. Concentration‐dependent inhibition of the melittin response was induced by preincubation with NIP‐121 (0.03 and 0.1 μm), isoprenaline (0.001 and 0.01 μm), aminophylline (30 and 100 μm) and hydrocortisone (100 and 300 μm). The effect of NIP‐121 was abolished by glibenclamide (1 μm). The inhibitory effect of NIP‐121 on the melittin response was greatly reduced by removing the epithelium while that of the isoprenaline, aminophylline or hydrocortisone was not changed. The inhibition of the melittin response by these drugs was similar to their inhibition of the contraction elicited by a low concentration (3 nm) of leukotriene D4 (LTD4) in the epithelium‐intact trachea. Inhibition of the LTD4 response by NIP‐121 was not observed in the epithelium‐denuded trachea. However, higher concentrations of NIP‐121 (0.3 and 1 μm) did inhibit LTD4‐induced contractions of epithelium‐denuded trachea. These findings suggest that melittin causes epithelium‐dependent contraction of the guinea‐pig isolated trachea which is mediated by products of lipoxygenase activity. NIP‐121 may inhibit the melittin response by activating glibenclamide‐sensitive potassium channels, which appear to be epithelium‐dependent (an indirect effect of NIP‐121 apart from its direct effect on the airway smooth muscle) while isoprenaline, aminophylline and hydrocortisone act directly to relax the trachealis smooth muscle.

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Section: Discussionsupporting

confidence: 64%

“…The effects of NIP-121 have been compared with those of the antiasthma drugs isoprenaline, aminophylline and hydrocortisone. We have previously reported that melittin caused contraction of the isolated guinea-pig trachea and that the response was similar to that of exogenously applied arachidonic acid (AA) (Yamamoto et al, 1990). …”

Section: Introductionmentioning

confidence: 99%

Influence of epithelium on the inhibition of melittin‐induced contraction of guinea‐pig isolated trachea by the potassium channel opener NIP‐121

Shikada

Tanaka

1993

British J Pharmacology

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“…Melittininduced effects were unaffected by bradykinin-receptor antagonists. Another difference between the effects of bradykinin and melittin is the sensitivity of the contractile response to melittin to 5-lipoxygenase inhibition (Yamamoto et al, 1990;Shikada & Tanaka, 1993). This observation is in agreement with the activation of phospholipase A2 by melittin, since arachidonic acid is the substrate of both cyclooxygenase and 5-lipoxygenase.…”

Section: Discussionsupporting

confidence: 74%

Involvement of B₂ receptors in the bradykinin‐induced relaxation of guinea‐pig isolated trachea

Silva

Amrani

Landry

1995

British J Pharmacology

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1 The aim of this study was to determine the receptor type and involvement of arachidonic acid metabolites in bradykinin-induced relaxation of the guinea-pig isolated trachea. 2 In the resting tracheal preparation, bradykinin (0.1 nM-30 LM induced a concentration-related contractile response (pD2 = 8.8 ± 0.3). The maximal tension (1056 ± 321 mg) was observed at 0.3 4M bradykinin. In contrast, when tracheal preparations were pre-contracted with histamine (30 LM leading to a half-maximum response), a concentration-related relaxation was observed with bradykinin. At the highest concentration of bradykinin used (3 LM), a reversal of 63 ± 13% of the contractile response to histamine was observed. Both effects of bradykinin were inhibited by the cyclo-oxygenase inhibitor, indomethacin (1I M). In concentration-response curves, melittin (1O nM-1 jM), a direct activator of phospholipase A2, mimicked both effects of bradykinin. The highest concentration of melittin used (1 tM), induced a tension of 813 ± 120 mg and led to the reversal of 41 ± 8% of the contractile response to histamine. The contractile effect of melittin was inhibited in the presence of both indomethacin (1 jM) and AA861 (1 jM), a 5-lipoxygenase inhibitor. . 4 These data demonstrate that bradykinin-induced relaxation of guinea-pig trachea occurs via the activation of bradykinin B2-receptors. The stimulation of B2-bradykinin receptors induces the activation of the cyclo-oxygenase pathway, leading either to contraction or relaxation depending on the tone of the trachea.

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“…NZ-107 inhibited antigen-induced contraction even in the presence ofserine-borate. We have observed that theeffect of FPL-55712 on the antigen-induced response was greatly reduced in the presence of serine-borate (Yamamoto et al 1991). NZ-107 moderately inhibited the contraction induced by synthetic LTC4 in the presence of serine-borate (Fig.…”

Section: Discussionmentioning

confidence: 73%

Effect of an Anti-SRS-A Agent, NZ-107, on Airway Responses Induced by Ovalbumin and A23187 in the Guinea-pig

Yamamoto

Shikada

Iwama

et al. 1991

Journal of Pharmacy and Pharmacology

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The effects of the anti-SRS-A agent NZ-107 on antigen-(ovalbumin) and calcium ionophore A23187-induced airway responses in the guinea-pig have been investigated. In the presence of 5 microM indomethacin, NZ-107 (3 microM) did not affect the peak response in ovalbumin-induced contraction but did inhibit the prolonged response following the peak response in the tracheal strip. A higher concentration of NZ-107 (10 microM) completely blocked both peak and prolonged responses. Inhibitory effects of NZ-107 on ovalbumin responses were less in the lung parenchymal strip. The potency of NZ-107 in inhibiting ovalbumin-induced tracheal contraction was not changed in the absence of indomethacin but was reduced in the presence of 45 mM serine-borate, an inhibitor of the conversion of LTC4 to LTD4. NZ-107 inhibited A23187-induced contractions in both tracheal and parenchymal strips but in both cases the inhibitory potency was less than that on ovalbumin response. NZ-107 was a more potent inhibitor of ovalbumin-induced SRS-A release than histamine release in lung fragments but was ineffective in inhibiting A23187-induced SRS-A and histamine release. NZ-107 at a concentration of 10 microM more effectively inhibited LTC4- and histamine-induced tracheal contractions than it did LTC4 in the presence of 45 mM serine-borate. These results suggest that NZ-107 selectively inhibits antigen-induced SRS-A responses in airway tissues of the guinea-pig.

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Arachidonate lipoxygenase inhibitors in guinea-pig isolated trachea. Effects on contractions to antigen and various agonists

Cited by 5 publications

References 14 publications

Influence of epithelium on the inhibition of melittin‐induced contraction of guinea‐pig isolated trachea by the potassium channel opener NIP‐121

Influence of epithelium on the inhibition of melittin‐induced contraction of guinea‐pig isolated trachea by the potassium channel opener NIP‐121

Involvement of B₂ receptors in the bradykinin‐induced relaxation of guinea‐pig isolated trachea

Effect of an Anti-SRS-A Agent, NZ-107, on Airway Responses Induced by Ovalbumin and A23187 in the Guinea-pig

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Arachidonate lipoxygenase inhibitors in guinea-pig isolated trachea. Effects on contractions to antigen and various agonists

Cited by 5 publications

References 14 publications

Influence of epithelium on the inhibition of melittin‐induced contraction of guinea‐pig isolated trachea by the potassium channel opener NIP‐121

Influence of epithelium on the inhibition of melittin‐induced contraction of guinea‐pig isolated trachea by the potassium channel opener NIP‐121

Involvement of B2 receptors in the bradykinin‐induced relaxation of guinea‐pig isolated trachea

Effect of an Anti-SRS-A Agent, NZ-107, on Airway Responses Induced by Ovalbumin and A23187 in the Guinea-pig

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Involvement of B₂ receptors in the bradykinin‐induced relaxation of guinea‐pig isolated trachea