?-endorphin-sensitive opioid receptors in the rat tail artery

Abstract

Isolated tail arteries of rats were perfused and field-stimulated every 2 min with 2 pulses at 1 Hz. Different opioid peptides depressed the contractile responses to stimulation; their concentration-response curves showed a maximum at about 40% inhibition. The rank order of potency of the peptides was β-endorphin (IC₅₀ = 97 nmol/1) ≅ BAM-22P > FK-33824 > DAGO > [d-Ala²,d-Leu⁵]-enkephalin ⩾ metorphamide > dynorphin A-(1-13) ≅[Met⁵]enkephalin. All these substances have in common a certain activity at opioid μ-receptors, although the enkephalins are preferential δ-, and the dynorphins preferential κ-agonists. However, the selective δ-agonist [d-Pen²,l-Pen⁵]enkephalin was ineffective at up to 10 μmol/l, and the κ-agonists ethylketocyclazocine and U-50488 acted only at concentrations higher than 3 μmol/l. Whereas the effects of β-endorphin, DAGO and [d-Ala²,d-Leu⁵]enkephalin could be reduced by the μ-preferential antagonist naloxone, the effects of ethylketocyclazocine and U-50488 were not changed. The δ-selective antagonist ICI 174864 did not influence the action of [d-Ala²,d-Leu⁵]enkephalin. Naloxone in a concentration (1 μmol/l) which nearly abolished the effect of DAGO 3 μmol/l, slightly enhanced responses to stimulation. Neither β-endorphin nor DAGO influenced vasoconstriction evoked by the application of noradrenaline or adenosine triphosphate; U-50488 reduced it. In arteries preincubated with [³H]noradrenaline DAGO depressed, whereas naloxone enhanced the tritium overflow and vasoconstriction evoked by field stimulation (0.4 Hz, 24 pulses every 14 min). In addition, naloxone antagonized the effect of DAGO. We suggest that the axon terminals of postganglionic sympathetic neurones in the rat tail artery possess β-endorphin-sensitive opioid receptors of the ɛ-type. The activation of these receptors by exogenous or endogenous opioids inhibits the release of the neuroeffector transmitter.