Effects of the functional elimination of sarcoplasmic reticulum on the manganese-dependent norepinephrine-induced contractions of the guinea pig vas deferens.

We investigated the effects of inhibitors of the sarcoplasmic reticulum (SR) functions on the tonic contractions induced by norepinephrine (NE) in the Ca(2+)-depleted Mn(2+)-loaded vas deferens of the guinea pig in the absence of both Ca2+ and Mn2+ (Mn(2+)-dependent NE-contraction). In control preparations without Ca(2+)-depletion and Mn(2+)-loading, either cyclopiazonic acid (CPA, 10 microM) or ryanodine (RYA, 3 microM) inhibited the initial phasic and tonic components but not the large phasic component of NE-induced contraction in normal medium containing 2.2 mM Ca2+. In contrast, CPA did not affect the Mn(2+)-dependent NE-contractions. The inhibitory effect of RYA slowly developed with each repetition of the Mn(2+)-dependent NE-contraction and the magnitude of the inhibition was slight. A23187 (10 microM) 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 Mn(2+)-loaded preparations, A23187 augmented the Mn(2+)-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 Mn(2+)-release from SR nor Mn(2+)-influx from the extracellular space contributes to the Mn(2+)-dependent NE-contractions. We concluded that NE induces Mn(2+)-dependent contractions by increasing Mn2+ sensitivity of contractile processes but not by increasing intracellular Mn2+ concentration.