The specific effect of Mn 2+ on the tonic components of receptor-mediated contractions in isolated vas deferens of the guinea pig

Abstract

Intracellular accumulation of Mn 2+ augmented the contractions induced by norepinephrine and acetylcholine in the guinea pig isolated vas deferens. Contractions repeatedly induced by norepinephrine, acetylcholine, or a high concentration of K + decreased depending on the incubation time in Ca 2+-free medium. The rate of decrease of all contractions was delayed by intracellularly accumulated manganese. In the Mn 2+-loaded preparations, the tonic components of the contractions induced by norepinephrine and acetylcholine, but not K +, were highly resistant to extracellular Ca 2+ elimination. Ryanodine abolished the initial phasic component but did not affect the tonic component of norepinephrine- and acetylcholine-contractions in Mn 2+-loaded preparations in Ca 2+-free medium. In Ca 2+-depleted preparations, the tonic contraction induced by norepinephrine was restored after the Mn 2+-loading procedure, and the magnitude of this tonic contraction was comparable to the tonic component of the norepinephrine contraction in the normal medium before Mn 2+ loading. The tonic contraction was reproducible in medium without either Mn 2+ or Ca 2+. These results suggested that intracellular Mn 2+ can support norepinephrine-induced tonic contractions. In the Ca 2+-depleted Mn 2+-loaded preparations, K + also induced a tonic contraction in the presence of extracellular Mn 2+. However, this contraction was much smaller than that induced by norepinephrine. These results suggested that intracellular Mn 2+ augmented contractions not only via an increase in intracellular Ca 2+ availability but also via the direct action of Mn 2+ on contractile mechanisms, and that this action is highly specific for developing and/or maintaining tonic contractions mediated by receptor activation in the guinea pig isolated vas deferens.