STIMULATION OF ENDOTHELIAL ANGIOTENSIN-CONVERTING ENZYME BY MORPHINE VIA NONOPIOID RECEPTOR-MEDIATED PROCESSES

In this study, we examined the influence of morphine and naloxone on t he enzymatic activity of different ecto-peptidases located on the surf ace of endothelial cells. Morphine increased in a concentration depend ent manner the degradation of Leu-enkephalin in cultivated bovine aort ic endothelial cells. Naloxone, a morphine antagonist, did not prevent this effect, but caused it as well. The enhanced Leu-enkephalin degra dation was due to an increase in the activity of angiotensin-convertin g enzyme (ACE), whereas the activity of other ecto-peptidases (aminope ptidase N and neutral endopeptidase) was not influenced. Despite a hig h non-specific binding of [H-3]-morphine, no specific opioid receptor binding on the endothelial cells could be detected. Autoradiographic i nvestigations with native, cryostat-sectioned cells demonstrated that [3H]-morphine was nearly exclusively located within the nuclei. The pr esent results suggests that the morphine effect concerning ACE activit y is not mediated via opioid receptors but presumably by interactions within the cell nucleus.