Blockade of alpha 2-adrenoceptors permits the operation of otherwise silent opioid kappa-receptors at the sympathetic axons of rabbit jejunal arteries.

We sought for presynaptic, release-inhibiting opioid receptors at the postganglionic sympathetic axons innervating the jejunal arteries of rabbits. Evoked excitatory junction potentials (e.j.p.s; trains of 15 pulses at 1 Hz) as well as evoked overflow of tritium after preincubation with [3H]-noradrenaline (trains of 120 pulses at 1 Hz) were used to estimate transmitter release. In otherwise untreated tissues ethylketocyclazocine reduced neither the e.j.p. amplitudes nor the evoked overflow of tritium; [Met5]-enkephalin depressed the evoked overflow of tritium. Ethylketocyclazocine reduced e.j.p. amplitudes, however, in tissues exposed to either yohimbine, tolazoline or phentolamine, but not in tissues exposed to prazosin. Ethylketocyclazocine also depressed the evoked overflow of tritium when yohimbine was present. The inhibition produced by ethylketocyclazocine in the presence of yohimbine was antagonized by (-)-3-furylmethyl)-alpha-noretazocine (MR 2266) but not by N,N-diallyl-Tyr-alpha-aminoisobutyric acid-alpha-aminoisobutyric acid-Phe-Leu-OH (ICI 174864). It is concluded that the sympathetic neurones of rabbit jejunal arteries possess presynaptic kappa-receptors in addition to the previously identified delta-receptors. The kappa-receptors become operative only when presynaptic alpha 2-adrenoceptors have been blocked.