Mechanism of tachyphylaxis on the inhibitory effect of manganese on agonist-induced contractions in the isolated vas deferens of the guinea pig.

In the isolated vas deferens of the guinea pig, the inhibitory effect of manganese (Mn2+) on contractions induced by norepinephrine decreased when the contractions were induced repeatedly in the presence of Mn2+. This phenomenon, "tachyphylaxis" to the inhibitory effect of Mn2+, was minimally observed when contractions were induced by acetylcholine. Contractions induced by acetylcholine as well as by norepinephrine in a Mn(2+)-free medium were augmented in preparations in which manganese had accumulated intracellularly by repetitive applications of high potassium in the presence of Mn2+. The magnitudes of their augmentation were dependent on the manganese contents of the preparations. The augmented contractions were remarkably resistant to the inhibitory effect of Mn2+ applied to the medium. These results suggest that intracellular manganese augments the contractions and this augmentation results in an apparent decrease in the inhibitory effect of Mn2+ in the medium.