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.