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In the isolated vas deferens of the guinea pig, the inhibitory effects of manganese (Mn2+) on the contractions induced by potassium (K+) were decreased when the contractions were induced repeatedly in the presence of Mn2+. This phenomenon appeared to be tachyphylaxis to the inhibitory effects of Mn2+. After the repetitive application of K+ with Mn2+, the phasic component of K(+)-induced contraction was restored, while the tonic component of this contraction and resting tone were augmented by the deprivation of extracellular Mn2+. When Mn2+ was applied during the tonic component of the K(+)-induced contraction, the phasic component of the next contraction induced by K+ in the absence of Mn2+ was slightly inhibited and the tonic component of the contraction was potentiated. When extracellular calcium concentration was increased, the inhibitory effect of Mn2+ on K(+)-induced contractions was reduced, while the tachyphylaxis to Mn2+ also appeared. Under this condition, the resting tone was markedly increased when the K(+)-induced contraction was repeated in the presence of Mn2+. In the calcium-free medium containing Mn2+, although K+ caused slow and monophasic contractions, the magnitude of the contractions was much smaller than that of the contractions induced in the normal medium containing Mn2+. These results suggest that the tachyphylaxis was not produced by the decrement of the inhibitory effects of Mn2+ on the contractions but by the augmenting effects of intracellularly accumulated Mn2+ and that these augmenting effects of Mn2+ are not due to the direct action on the contractile proteins but due to the indirect action of Mn2+ which increased the availability of Ca2+.

Tachyphylaxis to the inhibitory effect of manganese on potassium-induced contractions in the isolated vas deferens of the guinea pig.