Effects of the Functional Elimination of Sarcoplasmic Reticulum on the Manganese-Dependent Norepinephrine-Induced Contractions of the Guinea Pig Vas Deferens.

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We investigated the effects of inhibitors of the sarcoplasmic reticulum (SR) functions on the tonic contractions induced by norepinephrine (NE) in the Ca2+-depleted Mn2+-loaded was deferens of the guinea pig in the absence of both Ca2+ and Mn2+ (Mn2+-dependent NE-contraction). In control preparations without Ca2+ depletion and Mn2+ loading, either cyclopiazonic acid (CPA, 10μM) or ryanodine (RYA, 3μM) inhibited the initial phasic and tonic components but not the large phasic component of NE-induced contraction in normal medium containing 2.2mM Ca2+. In contrast, CPA did not affect the Mn2+-dependent NE-contractions. The inhibitory effect of RYA slowly developed with each repetition of the Mn2+-dependent NE-contraction and the magnitude of the inhibition was slight. A23187 (10μM) inhibited the NE-induced contractions of the control preparations in the same manner as CPA and RYA. Although A23187 did not induce contractions in the Mn2+-loaded preparations, A23187 augmented the Mn2+-dependent NE-contractions. The augmented tonic contractions returned to the resting level by washing NE and A23187. The augmentation remained for 3 successive contractions in the absence of A23187. However, the 2nd application of A23187 did not augment the contraction. These results suggest that neither Mn2+-release from SR nor Mn2+-influx from the extracellular space contributes to the Mn2+-dependent NE-contractions. We concluded that NE induces Mn2+-dependent contractions by increasing Mn2+ sensitivity ofcontractile processes but not by increasing intracellular Mn2+ concentration.

Effects of the Functional Elimination of Sarcoplasmic Reticulum on the Manganese-Dependent Norepinephrine-Induced Contractions of the Guinea Pig Vas Deferens.

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