Abstract
Maitotoxin (MTX), the most potent marine toxin, caused a dose-dependent contraction of the rabbit isolated aorta at 10-10-3 .times. 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 0.03-1.2 mM. In Ca2+-free solution, the contractile responses produced by reintroduction of Ca2+, Sr2+ or Ba2+ were potentiated after treatment with MTX (10-8 g/ml) and a high concentration of KCl (4 .times. 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. The dose-response curve for Ca2+ in the presence of A23,187 (3 .times. 10-5 M), a Ca ionophore, was not affected 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. MTX-induced contraction of the aorta was 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.