Effects of S14001 on adrenergic neuroeffector interaction in isolated canine saphenous veins

Abstract

The effects of (S)fluoro-6(morpholinyl-2 methoxy)-8-tetrahydro-1,2,3,4 quinoleine (S14001) on adrenergic neurotransmission in isolated canine saphenous veins were investigated in experiments which measured the accumulation, overflow and metabolism of 3H-norepinephrine. S14001 inhibited the accumulation of total tritium (3H-norepinephrine and 3H-metabolites of norepinephrine) in a concentration-dependent manner. Under basal conditions, S14001 increased tension and basal efflux of total tritium; the latter consisted predominantly of 3H-DOPEG. The increases in these parameters were not inhibited by desmethylimipramine (DMI). During electrical stimulation, S14001 increased the contraction and overflow of total tritium; the latter consisted predominantly of 3H-DOPEG. The increases in these parameters were inhibited by DMI. These experiments suggest that S14001 has dual effects on adrenergic neurotransmission in the canine saphenous vein: (a) an inhibitory action on the neuronal acumulation; and (b) a pharmacological displacement of the transmitter from adrenergic nerve terminals.