ETHANOL MODULATES NEUROPEPTIDE-DEGRADING AMINOPEPTIDASES AT SYNAPSE LEVEL IN CALCIUM-DEPENDENT CONDITIONS

María Dolores Mayas, María Jesús Ramírez-Expósito, María Jesús García, Pilar Carrera, José Manuel Martínez-Martos
2004 Alcohol and Alcoholism  
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 tyrosylaminopeptidase 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 Ca 2+ -containing or Ca 2+ -free medium. Results: Under basal
more » ... s: 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 Ca 2+ . However, in absence of Ca 2+ , 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 Ca 2+ . 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.
doi:10.1093/alcalc/agh052 pmid:15289202 fatcat:ceyih76ptvabzbohdzth37nsoa