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.