Vasoconstriction induced by zooxanthellatoxin-B, a polyoxygenated long- chain product from a marine alga

We found that zooxanthellatoxin-B from a symbiotic marine alga, Symbiodinium sp., caused a concentration-dependent contraction of the rabbit isolated aorta at concentrations of 10^-7 10^-5 M. Verapamil (10^-6 M) and mefenamic acid (10^-5 M) significantly attenuated the contractile response to zooxanthellatoxin-B at lower concentrations (10^-7 - 10^-6 M) but not at higher concentrations (3 X 10^-610^-5 M). The response to zooxanthellatoxin-B was partly inhibited by phentolamine (10^-6 M), whereas it was potentiated by ouabain (10^-5 M). Tetrodotoxin (10^-6 M), methysergide (10^-6 M), chlorpheniramine (10^-6 M) or indomethacin (3 X 10^-6 M), however, did not affect it. The zooxanthellatoxin-B-induced contraction was abolished by incubation in Ca²⁺-free solution. The contractile response increased in a concentration-dependent fashion with Ca²⁺ (0.03 and 10 mM) or Sr²⁺ (0.10 and 10 mM). After treatment with verapamil (10^-6 or 5 X 10^-6 M), the concentration-contractile response curves for Ca²⁺ and Sr²⁺ in the presence of zooxanthellatoxin-B were shifted to the right in parallel. MgCl₂ (10 mM) shifted the concentration- response curve for Ca²⁺ more markedly than did verapamil. Zooxanthellatoxin-B increased tissue Na⁺ and reduced tissue K⁺ contents in the aorta, suggesting that zooxanthellatoxin-B increases Na⁺ and K⁺ permeability across the plasma membrane. These results suggest that the zooxanthellatoxin-B-induced contraction of the aorta is caused mainly by a direct action on smooth muscle, i.e., an increase in Ca²⁺ permeability that occurs at least partly through voltage-sensitive Ca²⁺ channels as well as through nonselective cation channels in the cell membrane of smooth muscle.