Sarne Y, Rubovitch V, Fields A, Gafni M
Mauerberger Chair in Neuropharmacology, Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Israel.
Biochem Biophys Res Commun. 1998 May 8;246(1):128-31. doi: 10.1006/bbrc.1998.8582.
Opioid agonists either potentiate or suppress basal cAMP production in SK-N-SH cells. The inhibitory effect is mediated by PTX-sensitive GTP-binding proteins, while the stimulatory effect involves Ca++ entry and calmodulin activation. Both pathways can be activated simultaneously by opioid agonists. Low (nM) concentrations of either mu (DAMGO) or delta (DPDPE) selective opioids potentiate cAMP formation. At higher (100 nM) concentrations, however, a net suppression takes over; this suppression can be eliminated by PTX, and the underlying stimulatory effect is disclosed. Micromolar concentrations of either mu or delta selective agonists cross-activate the other (delta or mu) receptors, and augment the stimulatory pathway. The overall outcome (either stimulation or inhibition of cAMP production) is dependent on the balance between the two overlapping pathways, and can be modified by blocking either of the two opposing mechanisms.
阿片类激动剂可增强或抑制SK-N-SH细胞中的基础环磷酸腺苷（cAMP）生成。抑制作用由百日咳毒素（PTX）敏感的GTP结合蛋白介导，而刺激作用涉及钙离子内流和钙调蛋白激活。阿片类激动剂可同时激活这两条途径。低（纳摩尔）浓度的μ（DAMGO）或δ（DPDPE）选择性阿片类药物可增强cAMP形成。然而，在较高（100纳摩尔）浓度时，会出现净抑制；这种抑制可被PTX消除，潜在的刺激作用则会显现出来。微摩尔浓度的μ或δ选择性激动剂可交叉激活另一种（δ或μ）受体，并增强刺激途径。总体结果（对cAMP生成的刺激或抑制）取决于两条重叠途径之间的平衡，并且可以通过阻断两种相反机制中的任何一种来改变。
