RELAXING ACTIVITY OF 2 LINEAR DITERPENES FROM CYSTOSEIRA-BRACHYCARPA VAR BALEARICA ON THE CONTRACTIONS OF INTESTINAL PREPARATIONS

Eleganolone (1) and elegandiol (2), two linear diterpenes isolated fro m Cystoseira brachycarpa var. balearica, were tested on guinea-pig int estinal preparations. Both these compounds inhibited the contractile a ctivities of acetylcholine (Ach) and histamine (Hist) on ileum muscula ture; the relative pIC(50) values of eleganolone were found to be 4.60 +/- 0.03 and 4.84 +/- 0.20, respectively, while those of elegandiol w ere 4.71 +/- 0.18 and 5.18 +/- 0.01, respectively. Furthermore, 1 and 2 dose-dependently relaxed the same preparations precontracted with 30 0 mu M BaCl2 (pIC(50) = 4.34 +/- 0.18 for 1 and pIC(50) = 4.34 + 0.02 for 2) or with 60 mM KCl (pIC(50) = 4.73 +/- 0.18 and 4.47 +/- 0.06, r espectively). On colon smooth muscle, the diterpenes inhibited the spo ntaneous contractile tone and this effect was reversed by both methyle ne blue (3 x 10(-6) M) and haemoglobin (3 x 10(-6) M). Tetraethylammon ium (TEA), furosemide, N-omega- nitro L-arginine methyl ester (L-NAME) , indomethacin, alpha-chymotrypsin, and metoprolol were unable to bloc k the eleganolone and elegandiol relaxing action on colonic musculatur e, but rather potentiated this response. On the contrary, the beta(2)- blocker butoxamine partially inhibited the diterpenes activity. These results suggest that Cystoseira diterpenes act at a second messenger c yclase system rather than at a receptor level.