Interaction of prostaglandins and indomethacin with algesic substances
The isolated perfused rabbit ear connected to the body by its nerve only was used to investigate the modification of the algesic effect of bradykinin, substance P and acetylcholine (ACh) by indomethacin.
The effect of these algesic substances was inhibited by indomethacin in proportion to the dose and duration of infusion.
The factors by which the algesic effect was reduced by indomethacin and the factors by which it was enhanced by prostaglandin E1 were found to be correlated. The factors were greatest for bradykinin, intermediate for substance P and smallest for ACh, thus showing that the algesic effect of bradykinin is most dependent on the presence of prostaglandin E1.
In the presence of additional amounts of prostaglandin E1, indomethacin was able to reduce the algesic effect of bradykinin and ACh to some extent. This cannot be explained by blockade of the PG synthesis.
The vasoconstriction found after i.a. injection of bradykinin, substance P and PGF2α was partly inhibited by indomethacin. This was explained by a direct inhibitory influence of indomethacin on the vasoconstrictor effect of the prostaglandin or the algesic substances.
Indomethacin, due to a direct and reversible antagonism, reduced the contraction of the isolated guinea-pig ileum induced by PGE2 more than the contraction induced by bradykinin.
It is confirmed that indomethacin acts mainly by inhibition of biosynthesis of prostaglandins. An additional direct inhibition of prostaglandin-actions by indomethacin can, however, be seen under certain experimental conditions.
Key wordsPain Response Prostaglandins Bradykinin Substance P Acetylcholine Indomethacin
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