Gaudreau P, Lavigne G J, Quirion R
Neuroendocrinology Laboratory, Notre-Dame Hospital Research Center, University of Montreal, Canada.
Neuropeptides. 1990 May;16(1):51-5. doi: 10.1016/0143-4179(90)90029-x.
It has been reported that proglumide and L-364,718 potentiate opioid-induced antinociception. However, their mode of action in pain modulation is still not understood. To evaluate a possible interaction with opioid receptors, we determined the affinities of the CCK antagonists proglumide, lorglumide, benzotript and L-364,718 on mu, delta and kappa binding sites, using guinea pig brain crude synaptosome preparations. These affinities were compared to that of the central CCK binding site, using rat brain slide-mounted sections. At 100 microM, proglumide competed for 13% and 17% of mu and kappa binding sites, but did not interact with delta and CCK sites. At this concentration, lorglumide reduced mu, delta, kappa and CCK specific binding by 44%, 69%, 35% and 88%, whereas benzotript diminished it by 16%, 13%, 38% and 48%, respectively. L-364,718 did not interact with opioid receptors (assay limit of solubility, 10 microM) but had a high affinity for CCK binding sites (IC50, 126nM). The lack of selectivity of proglumide, lorglumide and benzotript for CCK receptors suggests that their reported ability to potentiate morphine analgesia may be related to an interaction with opioid receptors.
据报道，丙谷胺和L-364,718可增强阿片类药物诱导的镇痛作用。然而，它们在疼痛调节中的作用方式仍不清楚。为了评估与阿片受体的可能相互作用，我们使用豚鼠脑粗制突触体标本测定了CCK拮抗剂丙谷胺、氯谷胺、苯曲嗪和L-364,718对μ、δ和κ结合位点的亲和力。使用大鼠脑载玻片切片，将这些亲和力与中枢CCK结合位点的亲和力进行比较。在100微摩尔浓度下，丙谷胺竞争μ和κ结合位点的13%和17%，但不与δ和CCK位点相互作用。在此浓度下，氯谷胺使μ、δ、κ和CCK特异性结合分别降低44%、69%、35%和88%，而苯曲嗪分别使其降低16%、13%、38%和48%。L-364,718不与阿片受体相互作用（溶解度测定极限为10微摩尔），但对CCK结合位点具有高亲和力（IC50为126纳摩尔）。丙谷胺、氯谷胺和苯曲嗪对CCK受体缺乏选择性，这表明它们报道的增强吗啡镇痛的能力可能与与阿片受体的相互作用有关。
