Dual mechanism of ouabain action on noradrenaline output from guinea-pig vas deferens.

Isolated guinea-pig vas deferens was used to test the effects of varying the concentration of extracellular Na+, Ca2+ and Mg2+ and the influence of tetanic transmural stimulation and of tetrodotoxin on the ouabain-induced increase in noradrenaline output. The total amount of noradrenaline released by ouabain increased with increasing concentration of either Na+ (from 35 to 143 mM) or Ca2+ (from 0.3 to 2.5 mM). The rise in the ouabain-induced increase of noradrenaline output was retarded by increasing the concentration of either Ca2+ from 0.3 to 5 mM or Mg2+ from 1.2 to 20 mM. Tetanic transmural stimulation facilitated the occurrence of ouabain-induced noradrenaline output, while tetrodotoxin (5 X 10(-7) g/ml) greatly inhibited it. These results suggest that ouabain causes an increase in noradrenaline output through at least two different mechanisms, a tetrodotoxin-sensitive action potential and Na+-dependent Ca2+ influx resulting from the inhibition of the Na+-K+ pump.