PRESYNAPTIC OPIOID RECEPTOR SUBTYPES IN THE RABBIT EAR ARTERY

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  • 1 January 1985
    • journal article
    • research article
    • Vol. 232  (2) , 526-533
Abstract
In segments of rabbit ear arteries preincubated with [3H]noradrenaline [norepinephrine] Leu-enkephalin, D-Ala2-D-Leu-enkephalin and ethylketocyclazocine concentration dependently reduced the overflow of 3H and the vasoconstriction elicited by field stimulation (120 pulses every 14 min, 1 Hz, 0.3 msec pulse duration). The effects of Leu-enkephalin and ethylketocyclazocine were antagonized by naloxone which, given alone, increased the evoked overflow of 3H at the high concentration of 10 .mu.M. Morphine failed to produce inhibition, and at 100 .mu.M actually increased evoked 3H-overflow. Continued exposure to Leu-enkephalin desensitized the tissue to this opioid; there was no cross-desensitization to ethylketocyclazocine. In arteries not preincubated with [3H]noradrenaline, normorphine, fentanyl and morphiceptin did not change the vasoconstrictor response (5 pulses/min, 5 Hz, 0.3 msec pulse duration). Among various peptide agonists, Leu-enkephalin, D-Ala2-D-Leu-enkephalin and Met-enkephalin were the most potent inhibitors. In a series of peptides with C-terminal extensions of the Met-enkephalin chain, the potency decreased in the order Met-enkephalin > Met-enkephalin-Arg-Gly-Leu > Met-enkephalin-Arg-Phe > BAM-12P > .beta.-endorphin. In a series of peptides with C-terminal extensions of the Leu-enkephalin chain, the potency decreased in the order Leu-enkephalin > dynorphin1-13 > dynorphin1-9 > .alpha.-neo-endorphin > dynorphin1-6 > dynorphin1-6 > dynorphin1-17. The .DELTA. selective antagonist ICI 154129 counteracted the effect of Met-enkephalin but not that of dynorphin1-13, whereas naloxone counteracted the effect of either agonist. Given alone, high concentrations of naloxone and ICI 154129 as well as of the opioid antagonist (.sbd.)-MR 2266 (but not the nonantagonistic enantiomer (+)-MR 2267) enhanced the vasoconstrictor response. Naloxone and (.sbd.)-MR 2266 also enhanced the vasoconstriction elicited by exogenous noradrenaline, whereas Met-enkephalin selectively inhibited the response to electrical nerve stimulation. The postganglionic sympathetic neurons innervating the rabbit ear artery possess presynaptic opioid receptors of the .beta.- and .kappa.-, but not of the .mu.-types. The receptors do not appear to be targets of coreleased endogenous opioid peptides under the conditions of these experiments.