Presynaptic inhibitory opioid delta- and kappa-receptors in a branch of the rabbit ileocolic artery

Abstract

The largest rami caecales of the ileocolic artery (a branch of the mesenteric artery) were perfused at a constant rate of flow. Either vasoconstriction or the release of previously incorporated [3H]noradrenaline was measured. The following opioid agonists inhibited the vasoconstriction elicited by electrical field pulses (5 pulses at 10 Hz; EC50 values in brackets): [Leu5]enkephalin (596 nmol/l), [D-Ala2,D-Leu5]enkephalin (69 nmol/l), dynorphin-(1-13) (366 nmol/l) and ethylketocyclazocine (668 nmol/l). Fentanyl (up to 30 mumol/l) and normorphine (up to 100 mumol/l) caused at best minimal inhibition. The effects of [Leu5]enkephalin and dynorphin-(1-13) were antagonized by naloxone. Only the effect of [Leu5]enkephalin but not that of dynorphin-(1-13) was antagonized by the delta-selective antagonist ICI 154129. [Leu5]Enkephalin and dynorphin-(1-13) did not decrease the vasoconstrictor response to exogenous noradrenaline or ATP. In arteries preincubated with [3H]noradrenaline, electrical stimulation (50 pulses at 1 Hz) increased the outflow of tritium. The stimulation-evoked overflow was reduced by [Leu5]enkephalin and dynorphin-(1-13), and the effect of [Leu5]enkephalin was antagonized by naloxone. It is concluded that the postganglionic sympathetic neurons of the ramus caecalis possess presynaptic opioid receptors which, when activated, inhibited transmitter release. The receptors appear to be of the delta- and kappa- but not the mu-type.