The effect of MK-801 (dizocilpine) on the noradrenergic neurotransmission of the epididymal portion of rat vas deferens has been investigated. This drug potentiated the electrically induced responses (46.6% +/- 5.09 at a concentration of 3.7 microM) and the contractile effect of exogenous noradrenaline with a concentration-dependent reduction of EC50 (from 0.99 +/- 0.11 microM to 0.06 +/- 0.01 microM). Moreover, MK-801 alone induced spontaneous contractile responses that were abolished by prazosin, not reversed by N-methyl-D-aspartate (NMDA) + glycine and that did not appear in organs obtained from reserpinized rats. In addition, MK-801 inhibited the [3H]noradrenaline uptake in slices from rat vas deferens (IC50 = 1.79 +/- 0.06 microM). Since these effects took place in the presence of magnesium and were sodium-dependent, a direct participation of the NMDA receptor complex can be ruled out, pointing to the inhibition of the cathecolamine uptake systems in the postganglionic sympathetic nerve endings as the most feasible mechanism.