EFFECT OF ORAL MORPHINE AND NALOXONE ON PITUITARY-ADRENAL RESPONSE IN MAN INDUCED BY HUMAN CORTICOTROPIN-RELEASING HORMONE
EFFECT OF ORAL MORPHINE AND NALOXONE ON PITUITARY-ADRENAL RESPONSE IN MAN INDUCED BY HUMAN CORTICOTROPIN-RELEASING HORMONE
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DOI：
10.1530/acta.0.1140509
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发表时间：
1987-04-01
期刊：
影响因子：
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通讯作者：
WINKELMANN, W
中科院分区：
文献类型：
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作者：
ALLOLIO, B;SCHULTE, HM;WINKELMANN, W
为了进一步研究阿片类药物在调节垂体-肾上腺轴中的作用，我们研究了吗啡和纳洛酮对人促肾上腺皮质激素释放激素（hCRH）诱导的ACTH，免疫反应性(ir) β的影响。-内啡肽和皮质醇的释放协议:1。在给药前3小时口服吗啡或安慰剂缓释制剂30 mg（静脉0.1 mg） （N = 7）。在hCRH前5分钟给予纳洛酮（4mg，静脉注射）或安慰剂（N = 7）。在hCRH （N = 6）前15分钟开始纳洛酮（4mg静脉注射，随后连续输注6mg，持续75分钟）或安慰剂。hCRH在11.00 h（方案1,2）或17.00 h（方案3）注射。口服吗啡不仅可以抑制基础激素水平（P < 0.02），而且与安慰剂相比，hCRH的峰值反应(皮质醇：270 .+-。50 vs 559。80 nmol / l;Acth: 5.1 .+-。1.5 vs 13.1 .+-。2.7 pmol / l;红外度量。-内啡肽：48.5。8.7 vs 88。14 pmol / l;的意思。+ -。Sem, p < 0.02)。同样，与安慰剂相比，三种激素的最大增量变化和曲线下面积均显著减少（P < 0.05）。在早上服用4mg纳洛酮后，没有观察到对hCRH的显著激素变化。然而，与安慰剂相比，下午服用10mg纳洛酮导致hCGH反应的最大激素浓度更高（皮质醇：636 +-）。30 vs 437 .+-。63 nmol / l;Acth: 19.6 +-。4.4 vs . 8.7。1.1 pmol / l;红外度量。-内啡肽：180。44比94。18 pmol/l, P < 0.05)。大剂量纳洛酮对hcrh诱导的激素释放的影响支持了内源性阿片样物质通过相对纳洛酮抗性受体（.delta.-或.chi）对ACTH释放的生理显著抑制的概念。-受体)位于脑垂体水平。.mu。-激动剂吗啡可能通过抑制CRH增强因子作用于垂体上部位。
To further investigate the role of opioids in the regulation of the pituitary-adrenal axis we studied the effect of morphine and naloxone on human corticotropin-releasing hormone (hCRH)-induced ACTH, immunoreactive (ir) .beta.-endorphine, and cortisol release in normal subjects. Protocols: 1. 30 mg of a slow-release preparation of morphine or placebo was given orally 3 h prior to administration of hCRH (0.1 mg iv) (N = 7). 2. Naloxone (4 mg as bolus iv) or placebo was given 5 min prior to hCRH (N = 7). 3. Naloxone (4 mg iv as bolus followed by a continuous infusion of 6 mg over 75 min) or placebo was started 15 min prior to hCRH (N = 6). hCRH was injected at 11.00 h (protocol 1,2) or at 17.00 h (protocol 3). Oral morphine not only suppressed basal hormone levels (P < 0.02), but also the peak response to hCRH compared with placebo (cortisol: 270 .+-. 50 vs 559 .+-. 80 nmol/l; ACTH: 5.1 .+-. 1.5 vs 13.1 .+-. 2.7 pmol/l; ir .beta.-endorphin: 48.5 .+-. 8.7 vs 88 .+-. 14 pmol/l; mean .+-. SEM, P < 0.02). Similarly, the maximum incremental changes and the area under the curve were significantly reduced for all three hormones compared with placebo (P < 0.05). After 4 mg of naloxone in the morning, no significant hormonal changes in response to hCRH were observed. However, 10 mg of naloxone in the afternoon led to higher maximum hormone concentrations in response to hCGH compared with placebo (cortisol: 636 .+-. 30 vs 437 .+-. 63 nmol/l; ACTH: 19.6 .+-. 4.4 vs 8.7 .+-. 1.1 pmol/l; ir .beta.-endorphin: 180 .+-. 44 vs 94 .+-. 18 pmol/l, P < 0.05). The effect of high-dose naloxone on the hCRH-induced hormone release alone supports the concept of a physiologically significant inhibition of the ACTH release by endogenous opioids via receptors of relative naloxone resistance (.delta.- or .chi.-receptors) located at the pituitary level. The .mu.-agonist morphine may act at suprahypophyseal sites by inhibition of CRH potentiating factors.