Calcium-dependent modulation by ethanol of mouse synaptosomal pyroglutamylaminopeptidase activity under basal and K+-stimulated conditions

We studied the in vitro effects of ethanol (25, 50 and 100 mM) on pyrogluta myl aminopeptidase activity (pGluAP), which has been reported as thyrotroph in-releasing-hormone-degrading activity. pGluAP was measured in presence or absence of calcium, under basal and Kf stimulated conditions, in synaptoso mes and their incubation supernatant, using pyroglutamyl-beta -naphthylamid e as substrate. In basal conditions, in synaptosomes, pGluAP was inhibited by ethanol in a calcium-independent way. In the supernatant, the response d iffered depending on the concentration of ethanol. Depolarization with Kf m odified pGluAP in synaptosomes and supernatant depending on the presence or not of calcium. In synaptosomes, in absence of calcium, the activity was i nhibited at the highest concentrations of ethanol. In contrast, in the supe rnatant, under depolarizing conditions, ethanol increases pGluAP in absence of calcium. These changes may be in part responsible of the behavioural ch anges associated to alcohol intake. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.