[Influence of alcohol on brain aminopeptidases. An in vitro study].
BACKGROUND
It is well known the depressor effect of alcohol on several inhibitory nervous centres. This can be due to the inhibition that induces in the release of different type of neurotransmitters, and because alcohol can increase the membrane fluidity and changes the function of proteins inserted in the membrane. Several aminopeptidases (AP) have been described as enzymes that regulate the activity of peptide neurotransmitters. In the present work, the influence of alcohol (25, 50 and 100 mM) on several aminopeptidase activities (alanyl AP, arginyl AP, cystinyl AP, leucyl AP and tyrosyl AP) has been determined in synaptosomes obtained from the cortex of mouse, under basal and K+ stimulated conditions and their calcium dependence, in a non toxic in vitro model.


METHODS
AP activities were determined using aminoacyl ? naphthylamides as substrates. Non toxic in vitro model were demonstrated analyzing free radical generation, lipid peroxidation and oxidation of synaptosomal proteins. In addition, the bioenergetic behavior of synaptosomes was determined under different experimental protocols.


RESULTS
In basal conditions, alcohol produces a dose related inhibition of alanyl AP activity. The rest of activities show a biphasic behavior. In this way, depending on the concentration of alcohol used, aminopeptidases are inhibited or stimulated. Depolarization with K+ 25 mM leads to a decrease of alanyl AP and tyrosyl AP activities but does not change the rest of activities. The presence of alcohol under stimulated conditions produces the inhibition of all the enzymatic activities, specially with the highest concentrations used.


CONCLUSIONS
Alcohol modifies several aminopeptidase activities from synaptosomes of the cortex of mouse, acting in different ways under basal or stimulated conditions. These effects seem not to be related with degenerative events induced by alcohol. Therefore, a specific effect of this substance on the neurotransmisory/neuromodulatory systems mediated by neuropeptides must exist, modifying the enzymes that are responsible of their degradation.
Mayas
M D
MD
Departamento Ciencias de la Salud. Area Fisiología; Universidad de Jaén, Jaén, 23071, España.
Ramírez-Expósito
M J
MJ
García
M J
MJ
Ramírez
M
M
Martínez-Martos
J M
JM
D000626:Aminopeptidases / Q000378:metabolism*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000201:enzymology; D000431:Ethanol / Q000494:pharmacology*; D005609:Free Radicals; D015227:Lipid Peroxidation; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000187:drug effects; D010084:Oxidation-Reduction; D013574:Synaptosomes
D005609:Free Radicals; D000431:Ethanol; D000626:Aminopeptidases