Palytoxin-induced contraction and release of prostaglandins and norepinephrine in the aorta.
Mechanism of action of a potent marine toxin, palytoxin (PTX), in blood vessels was examined using rat and rabbit aortas. PTX in the concentrations of 10(-10) to 10(-8) M induced contraction in rat aortas. The rate of rise of contraction and the maximum contractile tension due to 10(-10) M PTX became greater when endothelium was removed from aortic strip. Methylene blue, 5 X 10(-6) M, also increased both the rate of rise and maximum tension. These results suggest that PTX may release a relaxing substance from endothelium which may inhibit the contraction induced by PTX itself. In contrast to this, the 10(-8) M PTX-induced contraction became smaller when endothelium was removed from the aorta. This contraction was partially inhibited by 10(-5) M indomethacin. Verapamil (10(-6) M) also inhibited a portion of this contraction and these inhibitors showed an additive inhibitory effect. Prazosin (10(-7) M) did not affect this contraction. Similar results were obtained in aortas without endothelium. Using thin-layer chromatography, it was found that PTX (10(-8) M) increased the release of prostaglandin E2, F2 alpha and 6-keto-prostaglandin F1 alpha from rat aortas with endothelium. In rabbit aortas, 10(-8) M PTX induced a contraction which was partially inhibited by 10(-6) M verapamil, 10(-5) M indomethacin or 10(-7) prazosin. The same concentration of PTX increased [3H]norepinephrine release from rabbit aortic adventitia.(ABSTRACT TRUNCATED AT 250 WORDS)
D000178:Acrylamides; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001688:Biological Products / Q000378:metabolism; D003064:Cnidarian Venoms / Q000494:pharmacology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009569:Nitric Oxide; D009638:Norepinephrine / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D014661:Vasoconstriction / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology; D000095702:Polyether Toxins
D000178:Acrylamides; D001688:Biological Products; D003064:Cnidarian Venoms; D007213:Indomethacin; D008751:Methylene Blue; D009569:Nitric Oxide; D009638:Norepinephrine; D011453:Prostaglandins; D014700:Verapamil; C010272:palytoxin; D000095702:Polyether Toxins