Ethanol modulates neuropeptide-degrading aminopeptidases at synapse level in calcium-dependent conditions.
OBJECTIVE
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.
Mayas
María Dolores
MD
Unit of Physiology, Department of Health Sciences, Faculty of Experimental and Health Sciences, University of Jaén, E-23071, Jaén, Spain.
Ramírez-Expósito
María Jesús
MJ
García
María Jesús
MJ
Carrera
Pilar
P
Martínez-Martos
José Manuel
JM
D000626:Aminopeptidases / Q000378:metabolism*; D000818:Animals; D018826:CD13 Antigens / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D010122:Cystinyl Aminopeptidase / Q000378:metabolism*; D000431:Ethanol / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D005625:Frontal Lobe / Q000187:drug effects / Q000201:enzymology; D007931:Leucyl Aminopeptidase / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009479:Neuropeptides / Q000378:metabolism*; D018847:Opioid Peptides / Q000378:metabolism; D011188:Potassium / Q000008:administration & dosage / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects*; D013574:Synaptosomes / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D009479:Neuropeptides; D018847:Opioid Peptides; D000431:Ethanol; D014443:Tyrosine; D000626:Aminopeptidases; D007931:Leucyl Aminopeptidase; D018826:CD13 Antigens; D010122:Cystinyl Aminopeptidase; C019721:aminopeptidase B; D011188:Potassium; D002118:Calcium