Antisense oligodeoxynucleotide to the CCKB receptor produces naltrindole- and [Leu5]enkephalin antiserum-sensitive enhancement of morphine antinociception.
Antisense oligodeoxynucleotide to the CCKB receptor produces naltrindole- and [Leu5]enkephalin antiserum-sensitive enhancement of morphine antinociception.
复制标题
CCKB 受体的反义寡脱氧核苷酸可产生纳曲吲哚和 [Leu5] 脑啡肽抗血清敏感性增强吗啡镇痛作用。
DOI：
10.1097/00001756-199412000-00049
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发表时间：
1994
期刊：
影响因子：
1.7
通讯作者：
Porreca,F
中科院分区：
文献类型：
--
作者：
Vanderah,TW;Lai,J;Yamamura,HI;Porreca,F
胆囊收缩素 (CCK) 已被证明可减弱吗啡的镇痛活性，而 CCK 拮抗剂可增强吗啡的镇痛活性，表明该肽可能充当阿片类药物系统的内源性调节剂。在这里，我们研究了与克隆小鼠 CCK B 受体（反义）5' 编码区互补的合成寡脱氧核苷酸 (oligo) 或错配寡核苷酸的给药对吗啡镇痛作用的影响。用 CCK B 反义寡核苷酸（而非错配寡核苷酸）对小鼠进行脑室内 (icv) 治疗 3 天，结果增强了 icv 吗啡的镇痛效力，如剂量效应曲线左移约 6 倍所示。在存在或不存在纳曲吲哚（一种阿片 δ 受体拮抗剂）以及存在或不存在针对 [Leu 5]-或 [Met 5] 脑啡肽的抗血清的情况下，研究吗啡对对照动物和 CCK B 反义治疗动物的镇痛作用。在用 CCK B 反义寡核苷酸预处理的小鼠中，吗啡的增强效力被 δ 选择性剂量的纳曲吲哚和 [Leu 5] 脑啡肽抗血清阻断，但不被 [Met 5] 脑啡肽阻断；纳曲吲哚或针对 [Leu 5] 脑啡肽或 [Met 5] 脑啡肽的抗血清单独给药时不会产生镇痛作用，并且不会改变对照小鼠中吗啡的镇痛作用。这些数据表明，CCK 可能通过 CCK B 受体发挥作用，强效抑制 [Leu 5] 脑啡肽或 [Leu 5] 脑啡肽样肽的释放。在存在 CCK B 受体阻断的情况下观察到的吗啡镇痛作用增强可能是众所周知的阿片样物质 5 激动剂增强吗啡镇痛作用的结果。
CHOLECYSTOKININ (CCK) has been shown to attenuate, while CCK antagonists enhance, the antinociceptive activity of morphine, suggesting that this peptide may act as an endogenous modulator of the opioid system. Here, we have investigated the effects of administration of a synthetic oligodeoxynucleotide (oligo) complementary to the 5'coding region of the cloned mouse CCK B receptor (anti-sense), or a mismatch oligo, on the antinociceptive effects of morphine. Intracerebroventricular (icv) treatment of mice with CCK B antisense, but not mismatch, oligo for 3 days resulted in an enhancement of the antinociceptive potency of icv morphine, as indicated by an approximately 6-fold leftward shift of the dose-effect curve. The antinociceptive effects of morphine in control and CCK B antisense-treated animals were investigated in the presence or absence of naltrindole, an opioid δ receptor antagonist, as well as in the presence or absence of antisera directed against either [Leu 5]-or [Met 5] enkephalin. The enhanced potency of morphine in mice pretreated with CCK B antisense oligo was blocked by a δ-selective dose of naltrindole and antisera to [Leu 5] enkephalin, but not [Met 5] enkephalin; naltrindole, or antisera towards [Leu 5] enkephalin or [Met 5] enkephalin did not produce antinociceptive effects when given alone and did not alter the antinociceptive actions of morphine in control mice. These data suggest that CCK may act via CCK B receptors to tonically inhibit the release of [Leu 5] enkephalin, or a [Leu 5] enkephalin-like peptide. The enhancement of morphine antinociception seen in the presence of blockade of the CCK B receptor may be the result of the well-known enhancement of morphine antinociception by opioid 5 agonists.