Presynaptic autoinhibition during rest and sodium-pump inhibition in isolated rat portal vein preparation.
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 X 10(-8)-10(-6) M) significantly reduced the nerve-evoked [3H]noradrenaline release. The IC50 value of L-noradrenaline proved to be 1.8 X 10(-7) M. Yohimbine (3 X 10(-7) M) 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(-4) M 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(-6) M) and yohimbine (3 X 10(-7) M) failed to significantly alter the nerve-evoked release. However, 3 X 10(-6) M 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.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D005246:Feedback; D008297:Male; D009433:Neural Inhibition; D009638:Norepinephrine / Q000378:metabolism*; D010525:Peripheral Nerves / Q000502:physiology*; D011169:Portal Vein / Q000294:innervation*; D011188:Potassium / Q000502:physiology; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D012964:Sodium / Q000502:physiology*
D011942:Receptors, Adrenergic, alpha; D012964:Sodium; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine