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Mechanism of action of bradykinin-induced release of prostaglandin E

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Summary

  1. 1.

    The mode of action of bradykinin-induced release/biosynthesis of prostaglandin E (PGE) was investigated using the method of the isolated perfused rabbit ear.

  2. 2.

    Phentolamine (1 μg/ml) hardly reduced the total amount of PGE released by bradykinin. Only in the first fraction (3 min) following bradykinin injection was PGE release significantly inhibited.

  3. 3.

    Papaverine (5–10 μg/ml) did not affect the bradykinin-induced PGE release but totally abolished the vasoconstriction evoked by the peptide.

  4. 4.

    Mepacrine (10 μg/ml) greatly inhibited the bradykinin-stimulated PGE release but did not reduce the conversion of arachidonic acid by cyclo-oxygenase into PGs when used in this concentration.

  5. 5.

    Phospholipase A2 — injected intra-arterially into the perfused rabbit ear — strongly stimulated the release of PGE. As with bradykinin, the phospholipase A2-induced PGE release was also significantly inhibited by meparcrine (10 μg/ml).

  6. 6.

    Bradykinin or arachidonic acid, even in high doses (20 or 100 μg respectively), were unable to promote the release of rabbit aorta contracting substance (RCS) from the rabbit ear.

  7. 7.

    PGs were not metabolized when injected intraarterially through the rabbit ear.

  8. 8.

    The results suggest that PGE release induced by bradykinin is hardly mediated via liberating catecholamines or the constricting vessel wall. It is concluded that bradykinin stimulates PGE release by selectively activating a phospholipase A2 without affecting cyclo-oxygenase and subsequent enzymes. The phosholipase A2 catalyzes the splitting of PG precursors from membrane phospholipids, before they are converted by the active PG synthetase system into PGs.

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  1. Institut für Experimentelle und Klinische Pharmakologie, Universitätsplatz 4, A-8010, Graz, Austria

    H. Juan

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A preliminary report was given on the Pharmacology Meeting Hannover 1976 [H. Juan and F. Lembeck: Naunyn-Schmiedeberg's Arch. Pharmacol. 294, R7, (1976c)].

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Juan, H. Mechanism of action of bradykinin-induced release of prostaglandin E. Naunyn-Schmiedeberg's Arch. Pharmacol. 300, 77–85 (1977). https://doi.org/10.1007/BF00505082

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