Stimulation of endothelial angiotensin-converting enzyme by morphine via non-opioid receptor mediated processes

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.