Alcohol and Alcoholism Advance Access published online on August 2, 2004
Alcohol and Alcoholism, doi:10.1093/alcalc/agh052
© 2004 by Medical Council on Alcohol
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1 Unit of Physiology, Department of Health Sciences, Faculty of Experimental and Health Sciences, University of Jaén, E-23071, Jaén, Spain
* To whom correspondence should be addressed. E-mail: jmmartos{at}ujaen.es.
Aims: To investigate the role of aminopeptidases in the pathways to peptides neurotransmission/neuromodulation ending in the actions of ethanol (EtOH) on the brain. Methods: The effects of EtOH on alanyl-, arginyl-, cystyl-, leucyl- and tyrosyl-aminopeptidase activities were studied under basal/resting and K+-stimulated conditions at the synapse level, using mouse frontal cortex synaptosomes and their incubation supernatant in a Ca2+-containing or Ca2+-free medium. Results: Under basal conditions, synaptosome aminopeptidase activities showed an inhibitory or biphasic response depending on the concentration of EtOH used and the aminopeptidase assayed, whereas supernatant activities showed a more complex response. Under K+-stimulated conditions, EtOH inhibited all synaptosome aminopeptidases assayed in presence of Ca2+. However, in absence of Ca2+, different responses were obtained depending on the concentration of EtOH used. In the supernatant, the highest concentration of EtOH inhibited the K+-stimulated increase on aminopeptidase activities, although the lowest concentration enhanced the release in presence of Ca2+. In absence of it, EtOH blocked the K+-stimulated decrease or increased the activity depending on the concentration of EtOH used. Conclusions: The changes on aminopeptidase activities induced by EtOH may reflect the functional status of their corresponding endogenous substrates. EtOH may influence opioid peptides, oxytocin, vasopressin and the brain renin-angiotensin system through their degrading enzymes.
Accepted February 8, 2004
Article
ETHANOL MODULATES NEUROPEPTIDE-DEGRADING AMINOPEPTIDASES AT SYNAPSE LEVEL IN CALCIUM-DEPENDENT CONDITIONS
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