Benoliel J J, Collin E, Mauborgne A, Bourgoin S, Legrand J C, Hamon M, Cesselin F
INSERM U 288, Neurobiologie Cellulaire et Fonctionnelle, Faculté de Médecine Pitié-Salpêtrière, Paris, France.
Brain Res. 1994 Aug 8;653(1-2):81-91. doi: 10.1016/0006-8993(94)90375-1.
The possible modulations by morphine and various opioids of the spinal release of cholecystokinin-like material (CCKLM) evoked by 30 mM K+ was studied in vitro, using slices of the dorsal part of the rat lumbar enlargement superfused with an artificial cerebrospinal fluid. Addition of the mu agonist, DAGO (0.1-10 microM), to the perfusing fluid produced a concentration-dependent decrease in the peptide release, which could be prevented by the preferential mu antagonist, naloxone. Complex modulations were induced by the delta agonist, DTLET, as this drug inhibited CCKLM release when added at 10 nM-3 microM to the perfusing fluid, but enhanced it at 10 microM. Both effects were preventable by the delta antagonists naltrindole and ICI 154129, suggesting that delta receptors, possibly of different subtypes, mediated the inhibition and stimulation by DTLET. Morphine also exerted a biphasic effect, as the alkaloid decreased CCKLM release at 0.01-0.1 microM and enhanced it at 10 microM. Morphine-induced inhibition was preventable by naloxone, whereas its stimulatory effect could be blocked by naltrindole and ICI 154129. Although inactive on its own on CCKLM release, the selective kappa 1 agonist U 50488H (1 microM) prevented the inhibitory effects of both DAGO (10 microM) and morphine (0.1 microM), suggesting the existence of interactions between kappa 1 and mu receptors within the dorsal zone of the rat spinal cord. These data indicate that low concentrations of morphine exert an inhibitory influence on spinal CCKergic neurons that depends on the stimulation of mu opioid receptors. The excitatory influence of 10 microM morphine likely results from the simultaneous stimulation of mu, delta and kappa receptors, as the inhibitory effect of mu receptor stimulation can be masked by that of kappa 1 receptors, allowing only the expression of a delta-dependent excitatory effect similar to that induced by 10 microM DTLET.
利用灌注人工脑脊液的大鼠腰膨大背侧切片，在体外研究了吗啡及各种阿片类药物对30 mM K⁺诱发的胆囊收缩素样物质（CCKLM）脊髓释放的可能调节作用。向灌注液中添加μ激动剂DAGO（0.1 - 10 μM）会使肽释放呈浓度依赖性降低，这种降低可被选择性μ拮抗剂纳洛酮阻断。δ激动剂DTLET诱导了复杂的调节作用，因为该药物在添加到灌注液中的浓度为10 nM - 3 μM时抑制CCKLM释放，但在10 μM时增强其释放。这两种作用均可被δ拮抗剂纳曲吲哚和ICI 154129阻断，提示可能不同亚型的δ受体介导了DTLET的抑制和刺激作用。吗啡也发挥了双相作用，生物碱在0.01 - 0.1 μM时降低CCKLM释放，在10 μM时增强其释放。吗啡诱导的抑制作用可被纳洛酮阻断，而其刺激作用可被纳曲吲哚和ICI 154129阻断。选择性κ₁激动剂U 50488H（1 μM）虽然自身对CCKLM释放无活性，但可阻断DAGO（10 μM）和吗啡（0.1 μM）的抑制作用，提示大鼠脊髓背侧区κ₁和μ受体之间存在相互作用。这些数据表明，低浓度吗啡对脊髓CCK能神经元发挥抑制作用，这依赖于μ阿片受体的刺激。10 μM吗啡的兴奋作用可能源于μ、δ和κ受体的同时刺激，因为μ受体刺激的抑制作用可被κ₁受体的作用掩盖，仅允许表达类似于10 μM DTLET诱导的δ依赖性兴奋作用。
