Presynaptic opioid receptors in the portal vein of the rabbit.

The effects of opioids on sympathetic neuroeffector transmission were studied in superfused strips of the portal vein of the rabbit. In the first series of experiments, the tissue was stimulated electrically every 10 min with 10 pulses at 8 Hz and a current strength of 200 mA. The contractions evoked were concentration dependently inhibited by the slightly kappa-selective agonist ethylketocyclazocine and by the delta-selective agonists [D-Ala2,D-Leu5]enkephalin (DADLE) and [D-Pen2,D-Pen5]enkephalin (DPDPLE). The mu-selective agonist [D-Ala2,NMePhe4,Gly-ol5]enkephalin (DAGO) had no effect. The estimated EC50 values for ethylketocyclazocine and DADLE were 5.5 X 10(-8) and 2.9 X 10(-8) mol/l, respectively. Naloxone shifted the concentration-response curves of ethylketocyclazocine and DADLE to the right; the estimated Kb values were (1.7 +/- 0.4) X 10(-8) mol/l and (2.9 +/- 0.8) X 10(-8) mol/l, respectively. The delta-selective antagonist ICI 174864 antagonized only the inhibitory effect of DADLE but not that of ethylketocyclazocine. In the second series of experiments, the tissue was preincubated with [3H]noradrenaline then superfused and stimulated electrically three times for 3 min at 1 Hz and a current strength of 100 mA. Ethylketocyclazocine and DADLE inhibited the evoked overflow of tritium. The inhibition produced by ethylketocyclazocine was antagonized by naloxone. Our results show for the first time that opioid agonists inhibit noradrenaline release and hence, neurogenic vasoconstriction in a vein. As in other cardiovascular tissues of the rabbit, the presynaptic opioid receptors are of the kappa- and delta- but not the mu-type.