Melzig M F, Heder G, Siems W E, Zipper J
Institute of Pharmacy, Humboldt-University, Berlin, Germany.
Pharmazie. 1998 Sep;53(9):634-7.
In this study, we examined the influence of morphine and naloxone on the enzymatic activity of different ecto-peptidases located on the surface of endothelial cells. Morphine increased in a concentration dependent manner the degradation of Leu-enkephalin in cultivated bovine aortic endothelial cells. Naloxone, a morphine antagonist, did not prevent this effect, but caused it as well. The enhanced Leu-enkephalin degradation was due to an increase in the activity of angiotensin-converting enzyme (ACE), whereas the activity of other ecto-peptidases (aminopeptidase N and neutral endopeptidase) was not influenced. Despite a high non-specific binding of [3H]-morphine, no specific opioid receptor binding on the endothelial cells could be detected. Autoradiographic investigations with native, cryostat-sectioned cells demonstrated that [3H]-morphine was nearly exclusively located within the nuclei. The present results suggests that the morphine effect concerning ACE activity is not mediated via opioid receptors but presumably by interactions within the cell nucleus.
在本研究中，我们检测了吗啡和纳洛酮对位于内皮细胞表面的不同外肽酶的酶活性的影响。吗啡以浓度依赖性方式增加了培养的牛主动脉内皮细胞中亮氨酸脑啡肽的降解。吗啡拮抗剂纳洛酮并未阻止这种作用，反而也导致了这种作用。亮氨酸脑啡肽降解增强是由于血管紧张素转换酶（ACE）活性增加，而其他外肽酶（氨肽酶N和中性内肽酶）的活性未受影响。尽管[3H]-吗啡有较高的非特异性结合，但在内皮细胞上未检测到特异性阿片受体结合。对天然的、经低温恒冷切片的细胞进行放射自显影研究表明，[3H]-吗啡几乎完全位于细胞核内。目前的结果表明，吗啡对ACE活性的作用不是通过阿片受体介导的，而是可能通过细胞核内的相互作用介导的。
