title: Ethanol modifies differently aspartyl- and glutamyl-aminopeptidase activities in mouse frontal cortex synaptosomes.
abstract: Aminopeptidase A activity (aspartyl aminopeptidase (AspAP) and glutamyl aminopeptidase (GluAP) exerts angiotensinase activity due to its relation to the metabolism of angiotensins in the regional brain renin-angiotensin system (RAS). This activity may also modify the free amino acid pool through the release of N-terminal acidic amino acids. Ethanol (EtOH) exerts profound effects on the brain, inducing important neurological damages. Our purpose is to study the influence of EtOH on AspAP and GluAP activities on basal and K(+)-stimulated conditions, at the synapse level. We used mouse frontal cortex synaptosomes and their incubation supernatant in a Ca(2+)-containing or Ca(2+)-free artificial cerebrospinal fluid. We evaluate the possible contribution of these enzymatic activities on brain blood pressure regulation through RAS and/or the free acidic amino acid pool. The results obtained are correlated with several parameters of oxidative stress, such as free radical generation, lipid peroxidation, and protein oxidation. Under basal conditions, in synaptosomes, EtOH inhibits AspAP and GluAP activities independently of Ca(2+). In the supernatant, however, EtOH differently modulates the two enzyme activities under the various concentrations. Under K(+)-stimulated conditions, EtOH inhibits the K(+)-stimulated increase on AspAP and GluAP differently depending on the presence or absence of Ca(2+) and the concentration of EtOH used. These results invalidate the idea that excess free acidic amino acids could be released by AspAP and GluAP to induce neurodegeneration. The changes in AspAP and GluAP activities as a consequence of EtOH administration and their role in the brain RAS are discussed.
authors.affiliation: 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.
authors.forename: María Dolores
authors.initials: MD
authors.lastname: Mayas
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Ramírez-Expósito
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: García
authors.forename: Manuel
authors.initials: M
authors.lastname: Ramírez
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Martínez-Martos
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000626:Aminopeptidases / Q000037:antagonists & inhibitors*; D000809:Angiotensins / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D017077:Culture Media, Conditioned; D000431:Ethanol / Q000494:pharmacology*; D005609:Free Radicals; D005625:Frontal Lobe / Q000187:drug effects* / Q000201:enzymology; D043384:Glutamyl Aminopeptidase; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D011188:Potassium / Q000494:pharmacology; D013574:Synaptosomes / Q000187:drug effects* / Q000201:enzymology
chemical_list: D000596:Amino Acids; D000809:Angiotensins; D017077:Culture Media, Conditioned; D005609:Free Radicals; D009419:Nerve Tissue Proteins; D000431:Ethanol; D000626:Aminopeptidases; D043384:Glutamyl Aminopeptidase; D011188:Potassium; D002118:Calcium