The specific effect of Mn2+ on the tonic components of receptor-mediated contractions in isolated vas deferens of the guinea pig.
Intracellular accumulation of Mn2+ 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 Ca2+ 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 Mn2+ loading. The tonic contraction was reproducible in medium without either Mn2+ or Ca2+. These results suggested that intracellular Mn2+ 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 Mn2+. However, this contraction was much smaller than that induced by norepinephrine. These results suggested that intracellular Mn2+ augmented contractions not only via an increase in intracellular Ca2+ availability but also via the direct action of Mn2+ 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.
Tsunobuchi-Ushijima
H
H
Department of Pharmacology, Kanazawa University, Japan.
Gomi
Y
Y
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D006168:Guinea Pigs; D008297:Male; D008345:Manganese / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D014649:Vas Deferens / Q000187:drug effects*
D002110:Caffeine; D008345:Manganese; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine