Presynaptic autoinhibition during rest and sodium-pump inhibition in isolated rat portal vein preparation

Abstract

In the presence of cocaine and corticosterone low-frequency (2 Hz) nerve stimulation evoked release of [ 3H]noradrenaline measured from isolated rat portal vein preparation. In normal Krebs solution exogenously applied l-noradrenaline (3 × 10 −8-10 −6M) significantly reduced the nerve-evoked [ 3H] noradrenaline release. The IC 50 value of l-noradrenaline proved to be1.8 × 10 −7M. Yohimbine (3 × 10 −7M) maximally blocked the alpha 2-adrenoceptors and enhanced nerve-evoked [ 3H]noradrenaline release. In the presence of 5.9 mM external K +, ouabain up to 10 −4M did not affect either the resting or the stimulation-evoked release of radioactivity from tissues. In the absence of external K + both the resting and the nerve-evoked release of [ 3H]noradrenaline increased markedly. When K + was readmitted to preparations which had been kept in K +-free solution both the resting and the stimulation-evoked [ 3H]noradrenaline release were greatly reduced temporarily. In K +-free solution l-noradrenaline (10 −6M) and yohimbine (3 × 10 −7M) failed to significantly alter the nerve-evoked release. However,3 × 10 −6M yohimbine in K +-free solution significantly increased the stimulation-evoked release of [ 3H]noradrenaline. It is concluded that presynaptic alpha 2-adrenoceptor-mediated “negative feed-back” is present in rat portal vein preparations which can be inhibited by the preferential alpha 2-adrenoceptor blocker, yohimbine. However, if the Na +-pump is inhibited (which by itself enhanced the transmitter release), presynaptic autoinhibition is more pronounced, since a high concentration of yohimbine is required to block it.