Contractile response of the rabbit aorta to maitotoxin, the most potent marine toxin.
Maitotoxin (MTX), the most potent marine toxin, caused a dose-dependent contraction of the rabbit isolated aorta at concentrations of 10(-10)-3 X 10(-8) g/ml. The dose-contractile response curve for MTX was shifted to the right in a parallel manner by verapamil (10(-6) M), was slightly shifted to the right by phentolamine (10(-6) M) and was not or little affected by tetrodotoxin, methysergide, chlorpheniramine or indomethacin. The MTX-induced contraction was abolished by incubation in Ca2+-free medium and was increased in a linear fashion with Ca2+ concentrations between 0.03 and 1.2 mM. In Ca2+-free solution, the contractile responses produced by re-introduction of Ca2+, Sr2+ or Ba2+ were potentiated after treatment with MTX (10(-8) g/ml.) and a high concentration of KCl (4 X 10(-2) M). After treatment with verapamil (10(-7)-10(-6) M), the dose-contractile response curve for Ca2+, Sr2+ or Ba2+ in the presence of MTX or KCl was shifted to the right in a parallel manner, indicating competitive antagonism. But the dose-response curve for Ca2+ in the presence of A23187 (3 X 10(-5) M), a Ca ionophore, was not affected at all by verapamil (10(-6) M). The tissue Ca content of the aorta was increased 31% by treatment with MTX (10(-8) g/ml.). This effect of MTX was markedly inhibited in the presence of verapamil. On the basis of these results, it is suggested that the MTX-induced contraction of the aorta is caused mainly by a direct action on smooth muscle, possibly due to an increase in Ca2+ permeability which occurred through voltage-sensitive Ca2+ channels in the smooth muscle cell membrane.
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002122:Calcium Chloride / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008274:Magnesium / Q000494:pharmacology; D015636:Magnesium Chloride; D008297:Male; D008387:Marine Toxins / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D035964:Oxocins; D010646:Phentolamine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology; D000095702:Polyether Toxins
D000001:Calcimycin; D002118:Calcium; D002122:Calcium Chloride; D008274:Magnesium; D015636:Magnesium Chloride; D008387:Marine Toxins; D035964:Oxocins; D010646:Phentolamine; D011189:Potassium Chloride; D000254:Sodium-Potassium-Exchanging ATPase; D014700:Verapamil; C020394:maitotoxin; D000095702:Polyether Toxins