Modification by Cholecystokinin Octapeptide of the Binding ofμ‐, δ‐, and K‐Opioid Receptors
Modification by Cholecystokinin Octapeptide of the Binding ofμ‐, δ‐, and K‐Opioid Receptors
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DOI：
10.1111/j.1471-4159.1990.tb03149.x
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发表时间：
1990-10
影响因子：
4.7
通讯作者：
Xiao-Jing Wang;Jisheng Han
中科院分区：
文献类型：
--
作者：
Xiao-Jing Wang;Jisheng Han
摘要：先前的研究表明，八肽胆囊收缩素（CCK-8）抑制阿片受体与通用阿片受体激动剂[3 H]埃托啡的结合。在本研究中，使用μ-{[酪氨酰-3，5-3H][d-Ala 2，MePhe 4，Gly-ol 5]脑啡肽（[3 H]DAGO）}、δ-{[酪氨酰-3，5-3H][d-Pen 2，5]脑啡肽（[3 H]DPDPE）}和k-（[3 H]U69，593）阿片受体的高选择性氚标记激动剂来阐明CCK-8抑制大鼠脑匀浆中哪种类型的阿片受体。在竞争实验中，CCK-8抑制[3 H]DAGO和[3 H]U69，593与相应阿片受体的结合，但不抑制[3 H]DPDPE与相应阿片受体的结合。CCK拮抗剂丙谷胺（1 μmol/L）可阻断此作用。在饱和实验中。CCK-8在0.1 nmol/L ~ 1 μmol/L浓度范围内降低[3 H]DAGO结合位点的Bmax，但不影响KD;另一方面，CCK-8增加[3 H]U69，593结合的KD，但不改变Bmax。结果表明，CCK-8通过激活CCK受体抑制μ-和K-阿片受体的结合。
Abstract: 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 μ‐ {[tyrosyl‐3,5‐3H][d‐Ala2,MePhe4,Gly‐ol5]enkephalin ([3H]DAGO)}, δ‐ {[tyrosyl‐3,5‐3H][d‐Pen2,5]enkephalin ([3H]DPDPE)}, and k‐ ([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 μmol/L. In the saturation experiments. CCK‐8 at concentrations of 0.1 nmol/L to 1 μmol/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 μ‐ and K‐opioid receptors via the activation of CCK receptors.