Chronic ethanol intake modifies pyrrolidon carboxypeptidase activity in mouse frontal cortex synaptosomes under resting and K+ -stimulated conditions: role of calcium.
Pyrrolidon carboxypeptidase (Pcp) is an omega peptidase that removes pyroglutamyl N-terminal residues of peptides such as thyrotrophin-releasing hormone (TRH), which is one of the neuropeptides that has been localized into many areas of the brain and acts as an endogenous neuromodulator of several parameters related to ethanol (EtOH) consumption. In this study, we analysed the effects of chronic EtOH intake on Pcp activity on mouse frontal cortex synaptosomes and their corresponding supernatant under basal and K+ -stimulated conditions, in presence and absence of calcium (Ca2+) to know the regulation of Pcp on TRH. In basal conditions, chronic EtOH intake significantly decreased synaptosomes Pcp activity but only in absence of Ca2+. However, supernatant Pcp activity is also decreased in presence and absence of calcium. Under K+-stimulated conditions, chronic EtOH intake decreased synaptosomes Pcp activity but only in absence of Ca2+, whereas supernatant Pcp activity was significantly decreased only in presence of Ca2+. The general inhibitory effect of chronic EtOH intake on Pcp activity suggests an inhibition of TRH metabolism and an enhancement of TRH neurotransmitter/neuromodulator functions, which could be related to putative processes of tolerance to EtOH in which TRH has been involved. Our data may also indicate that active peptides and their degrading peptidases are released together to the synaptic cleft to regulate the neurotransmitter/neuromodulator functions of these peptides, through a Ca2+ -dependent mechanism.
Mayas
María Dolores
MD
Fundación IMABIS, Hospital Carlos Haya, Málaga, Spain.
Ramírez-Expósito
María Jesús
MJ
García-López
María Jesús
MJ
Carrera
María Pilar
MP
Martínez-Martos
José Manuel
JM
D000818:Animals; D001522:Behavior, Animal; D002118:Calcium / Q000502:physiology*; D002492:Central Nervous System Depressants / Q000008:administration & dosage*; D000431:Ethanol / Q000008:administration & dosage*; D005625:Frontal Lobe / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011188:Potassium / Q000494:pharmacology; D011751:Pyroglutamyl-Peptidase I / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D002492:Central Nervous System Depressants; D000431:Ethanol; D011751:Pyroglutamyl-Peptidase I; D011188:Potassium; D002118:Calcium