Action of polygodial, a sesquiterpene isolated from Drymis winteri, in the guinea-pig ileum and trachea 'in vitro'.

Abstract

This study describes the action of the sesquiterpene polygodial, the major constituent isolated from the bark of Drymis winteri in the guinea pig ileum and trachea in vitro. Polygodial (5 to 128 microM), added for 20 min, did not affect the resting tone of the preparations, but caused graded inhibition, associated in some cases with rightward displacement of the acetylcholine, histamine (1 nM to 10 microM), bradykinin (0.1 nM to 1 microM) and KCl (1 to 100 mM)-contraction response curves. When assessed in the guinea-pig trachea, polygodial (5 to 342 microM) caused significant inhibition of bradykinin (10 pM to 1 microM), 9,11-dideoxy-9alpha,11alpha-methano-epoxy prostaglandin F2alpha (0.1 to 1000 nM) and KCl (1 to 100 mM)-induced contractions, although the action against bradykinin was not concentration-dependent. Polygodial (5 to 80 microM) caused a small but significant shift to the right of substance P and also the selective agonist of tachykinin NK2 receptor [beta-Ala8]neurokinin A-(4-10)-induced contractions in guinea pig trachea. This action of polygodial seems to be quite selective towards tachykinin NK2 receptors since up to 432 microM, polygodial had no effect against contraction caused by tachykinin NK1 receptor agonist, substance P methyl ester. When tested in the guinea-pig trachea from animals which had been actively sensitised to ovalbumin, polygodial (30 to 40 microM) caused time and concentration-dependent inhibition of ovalbumin-mediated contraction. In addition, polygodial (85 to 342 microM) inhibited contraction induced by compound 48/80 (1 to 1000 microg/ml), in the guinea-pig trachea from non-sensitised animals. These findings and those from our previous study are consistent with the notion that the main sesquiterpene polygodial isolated from the bark of D. winteri is responsible for most, if not all, of the relevant pharmacological action reported previously for the extract of this plant. Thus, polygodial could be of potential value in the development of a new drug for the treatment of asthma, allergy and other inflammatory processes.