Opioid effects on spinal [ 3H]5-hydroxytryptamine release are not related to their antinociceptive action

Abstract

Several opioid compounds were evaluated for an ability to modulate the K +-stimulated release of [ 3H]serotonin ([ 3H]5-hydroxytryptamine, [ 3H]5-HT) from rat spinal cord synaptosomal and tissue slice preparations. Selective κ-opioid receptor agonists depressed K +-stimulated release of the radiolabelled transmitter from both tissue preparations, an effect which was reversed by norbinaltorphimine. Conversely, the selective μ- and δ-opioid receptor agonists [ d-Ala 2,NMePhe 4,Gly-ol 5]enkephalin (DAMGO) and [ d-Pen 2, d-Pen 5]enkephalin (DPDPE), respectively, enhanced the K +-stimulated release of [ 3H]5-HT. This effect was only seen using the tissue slice preparation. When used at concentrations near its reported K d for μ-opioid receptors, the selective μ-opioid receptor antagonist d-Phe-Cys-Tyr- d-Trp-Orn-Thr-Pen-Thr-NH 2 (CTOP) blocked the action of DAMGO, but had no effect on the action of DPDPE. However, higher concentrations of CTOP, as well as all effective concentrations of selective δ-opioid receptor antagonists, blocked the action of both DAMGO and DPDPE. All agonist effects on spinal 5-HT release, regardless of the tissue preparation, were only seen at high (μM) concentrations. Moreover, effects of the opioid agonists were not consistent with the reported involvement of spinal 5-HT neurotransmission in the mediation of their antinociceptive action. Thus, the ability of opioids to modulate spinal 5-HT release appears to be of minimal physiological significance.