Suarez-Roca H, Maixner W
Department of Pharmacology, University of North Carolina, Chapel Hill 27599-7455.
Eur J Pharmacol. 1992 Dec 8;229(1):1-7. doi: 10.1016/0014-2999(92)90278-c.
The release of substance P (SP) from spinal dorsal horn slices is partially inhibited by micromolar concentrations of selective delta-opioid receptor agonists. In the present study, we have examined the effect of nanomolar concentrations of [D-Pen2,D-Pen5]enkephalin (DPDPE, delta-opioid receptor agonist) and low micromolar of concentrations morphine on K(+)-evoked SP release from rat trigeminal nucleus caudalis (TNC) slices. DPDPE and morphine inhibited SP release with an apparent maximal effect at 3 nM and at 3 microM, respectively. DPDPE and morphine produced U-shaped concentration-response curves that were completely autoinhibited at 100 nM DPDPE and 1 microM morphine. The inhibition of SP release produced by 3 nM DPDPE and 3 microM morphine was blocked by the opioid receptor antagonists naloxone (30 nM; non-selective) and ICI 174,864 (0.3 microM; delta-selective) but not by nor-binaltorphimine (3 nM n-BNI; kappa-selective), naloxonazine (1 nM; micro 1-selective) or beta-funaltrexamine (20 nM beta-FNA; mu-selective). These findings indicate that delta-opioid receptor-mediated inhibition of SP release from TNC can be achieved by nanomolar concentrations of selective delta-opioid receptor agonists. Activation of delta-opioid receptors by morphine might be involved in the residual analgesia observed after mu 1-opioid receptor blockade and in the analgesia produced by high doses of morphine.
微摩尔浓度的选择性δ-阿片受体激动剂可部分抑制脊髓背角切片中P物质（SP）的释放。在本研究中，我们检测了纳摩尔浓度的[D- Pen2，D- Pen5]脑啡肽（DPDPE，δ-阿片受体激动剂）和低微摩尔浓度的吗啡对大鼠三叉神经尾核（TNC）切片中钾离子诱发的SP释放的影响。DPDPE和吗啡分别在3 nM和3 μM时对SP释放产生明显的最大抑制作用。DPDPE和吗啡产生了U形浓度-反应曲线，在100 nM DPDPE和1 μM吗啡时完全出现自身抑制。3 nM DPDPE和3 μM吗啡对SP释放的抑制作用被阿片受体拮抗剂纳洛酮（30 nM；非选择性）和ICI 174,864（0.3 μM；δ-选择性）阻断，但未被去甲双丙吗啡（3 nM n-BNI；κ-选择性）、纳洛嗪（1 nM；μ1-选择性）或β-氟奈曲明（20 nM β-FNA；μ-选择性）阻断。这些结果表明，纳摩尔浓度的选择性δ-阿片受体激动剂可实现δ-阿片受体介导的对TNC中SP释放的抑制。吗啡对δ-阿片受体的激活可能参与了μ1-阿片受体阻断后观察到的残余镇痛以及高剂量吗啡产生的镇痛作用。
