Wang X J, Han J S
Department of Physiology, Beijing Medical University, People's Republic of China.
J Neurochem. 1990 Oct;55(4):1379-82. doi: 10.1111/j.1471-4159.1990.tb03149.x.
Previous study has shown that cholecystokinin (CCK) octapeptide (CCK-8) suppressed the binding of opioid receptors to the universal opioid agonist [3H]etorphine. In the present study, highly selective tritium-labeled agonists for the mu-[(tryrosyl-3,5-3H][D-Ala2,MePhe4,Gly-ol5]enkephalin ([3H]DAGO], delta- ([tyrosyl-3,5-3H][D-Pen2,5]enkephalin ([3H]DPDPE], and kappa- ([3H]U69,593) opioid receptors were used to clarify which type(s) of opioid receptor in rat brain homogenates is suppressed by CCK-8. In the competition experiments, CCK-8 suppressed the binding of [3H]DAGO and [3H]U69,593 but not that of [3H]DPDPE to the respective opioid receptor. This effect was blocked by the CCK antagonist proglumide at 1 mumol/L. In the saturation experiments, CCK-8 at concentrations of 0.1 nmol/L to 1 mumol/L decreased the Bmax of [3H]DAGO binding sites without affecting the KD; on the other hand, CCK-8 increased the KD of [3H]U69,593 binding without changing the Bmax. The results suggest that CCK-8 inhibits the binding of mu- and kappa-opioid receptors via the activation of CCK receptors.
先前的研究表明，胆囊收缩素（CCK）八肽（CCK-8）可抑制阿片受体与通用阿片激动剂[3H]埃托啡的结合。在本研究中，使用了针对μ-（[酪氨酸-3,5-3H][D-丙氨酸2，甲基苯丙氨酸4，甘醇5]脑啡肽（[3H]DAGO）、δ-（[酪氨酸-3,5-3H][D-青霉胺2,5]脑啡肽（[3H]DPDPE）和κ-（[3H]U69,593）阿片受体的高选择性氚标记激动剂，以阐明大鼠脑匀浆中哪种类型的阿片受体被CCK-8抑制。在竞争实验中，CCK-8抑制了[3H]DAGO和[3H]U69,593与各自阿片受体的结合，但不抑制[3H]DPDPE的结合。这种作用在1μmol/L的CCK拮抗剂丙谷胺存在时被阻断。在饱和实验中，浓度为0.1nmol/L至1μmol/L的CCK-8降低了[3H]DAGO结合位点的Bmax，而不影响KD；另一方面，CCK-8增加了[3H]U69,593结合的KD，而不改变Bmax。结果表明，CCK-8通过激活CCK受体抑制μ-和κ-阿片受体的结合。
