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(-6)-10(-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.
Department of Pharmaceutical Molecular Biology, Faculty of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
T
T
Moriya
Y
Y
Ishida
H
H
Nakamura
T
T
Asari
A
A
Murai
Y
Y
Ohizumi
D000818:Animals; D001011:Aorta; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D002463:Cell Membrane Permeability / Q000187:drug effects; D004141:Dinoflagellida / Q000737:chemistry; D056890:Eukaryota / Q000737:chemistry; D066298:In Vitro Techniques; D008387:Marine Toxins / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D011090:Polyenes / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D011817:Rabbits; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013552:Swine; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D008387:Marine Toxins; D011090:Polyenes; D014662:Vasoconstrictor Agents; C081401:zooxanthellatoxin B; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium