Monroe P J, Kradel B K, Smith D L, Smith D J
Department of Anesthesiology, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown 26506-9134.
Eur J Pharmacol. 1995 Jan 5;272(1):51-6. doi: 10.1016/0014-2999(94)00623-f.
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 kappa-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 mu- and delta-opioid receptor agonists [D-Ala2,NMePhe4,Gly-ol5]enkephalin (DAMGO) and [D-Pen2,D-Pen5]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 Kd for mu-opioid receptors, the selective mu-opioid receptor antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (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 delta-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 (microM) 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.
对几种阿片类化合物调节大鼠脊髓突触体和组织切片制剂中K⁺刺激的[³H]5-羟色胺（[³H]5-HT）释放的能力进行了评估。选择性κ阿片受体激动剂抑制了两种组织制剂中K⁺刺激的放射性标记递质的释放，诺宾那托啡能逆转这种作用。相反，选择性μ和δ阿片受体激动剂[D-Ala²，NMePhe⁴，Gly-ol⁵]脑啡肽（DAMGO）和[D-Pen²，D-Pen⁵]脑啡肽（DPDPE）分别增强了K⁺刺激的[³H]5-HT释放。这种作用仅在使用组织切片制剂时观察到。当以接近其报道的μ阿片受体Kd的浓度使用时，选择性μ阿片受体拮抗剂D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH₂（CTOP）阻断了DAMGO的作用，但对DPDPE的作用没有影响。然而，更高浓度的CTOP以及所有有效浓度的选择性δ阿片受体拮抗剂都阻断了DAMGO和DPDPE的作用。无论组织制剂如何，所有阿片激动剂对脊髓5-HT释放的作用仅在高（微摩尔）浓度下观察到。此外，阿片激动剂的作用与报道的脊髓5-HT神经传递参与其镇痛作用的介导不一致。因此，阿片类药物调节脊髓5-HT释放的能力似乎具有最小的生理意义。
