Effects of lyngbyatoxin A from the blue-green alga Lyngbya majuscula on rabbit aorta contractions.
The contractile effects of the tumor promoter and protein kinase C activator, lyngbyatoxin A, were studied in rabbit aorta rings. Contractions to 1 microM lyngbyatoxin A developed slowly, becoming maximal in approximately 3 hr. Contractions were not altered by 1 microM indomethacin, 1 microM nordihydroguaiaretic acid, or by endothelium removal, indicating that they did not involve contracting or relaxing substances from the epithelium. The contractions were also unaltered by calcium deletion from the medium and by 1 microM verapamil. Removal of adventitia did not alter contractions to lyngbyatoxin A, indicating that they did not involve release of norepinephrine or other neural vasoconstrictors. Previous contraction by norepinephrine in calcium-free medium containing a calcium-sequestering agent did not reduce subsequent lyngbyatoxin A contractions, indicating that they did not utilize the easily depleted intracellular calcium pool utilized by norepinephrine. Partial contraction with lyngbyatoxin A did not prevent contraction of the rings to norepinephrine. Contractions to lyngbyatoxin A in calcium-free medium did not differ from those obtained in calcium-free medium with 80 mM potassium chloride, indicating the contractions involved pharmacomechanical coupling. Contractions to both 1 microM lyngbyatoxin A and to 3 microM norepinephrine were depressed 18 hr after greater than 2 hr exposure to 1 microM lyngbyatoxin A (44 and 27%, respectively). Thus, lyngbyatoxin A contracts the rabbit aorta by an extracellular and intracellular calcium-, endothelium- and neuron-independent mechanism similar to the protein kinase C activating phorbol esters.
Robinson
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CP
College of Pharmacy, University of Oklahoma, Oklahoma City 73190.
Franz
D R
DR
Bondura
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ME
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D000458:Cyanobacteria / Q000737:chemistry*; D066298:In Vitro Techniques; D008235:Lyngbya Toxins / Q000494:pharmacology*; D008297:Male; D008387:Marine Toxins / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D011817:Rabbits; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D008235:Lyngbya Toxins; D008387:Marine Toxins; D013755:Tetradecanoylphorbol Acetate; C019457:lyngbyatoxin A; D002118:Calcium; D009638:Norepinephrine