Alcohol and Alcoholism Advance Access originally published online on August 2, 2004
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Alcohol & Alcoholism Vol. 39, No. 5, pp. 393-405, 2004
Alcohol & Alcoholism Vol. 39, No. 5 © Medical Council on Alcohol 2004; all rights reserved
ETHANOL MODULATES NEUROPEPTIDE-DEGRADING AMINOPEPTIDASES AT SYNAPSE LEVEL IN CALCIUM-DEPENDENT CONDITIONS
Unit of Physiology, Department of Health Sciences, Faculty of Experimental and Health Sciences, University of Jaén, E-23071, Jaén, Spain
* Author to whom correspondence should be addressed at: Unit of Physiology, Department of Health Sciences, Faculty of Experimental and Health Sciences, University of Jaén, Paraje Las Lagunillas s/n, E-23071, Jaén, Spain. Tel.: +34 953 002 600; Fax: +34 953 012 141; Email: jmmartos{at}ujaen.es
(Received 7 February 2002; accepted 8 February 2004)
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.