Subchronic haloperidol administration decreases aminopeptidase N activity and [Met5]enkephalin metabolism in rat striatum and cortex.
Previously we have shown that subchronic intraperitoneal (i.p.) administration of haloperidol decreases the degradation of [Met5]enkephalin by regional brain slices (Waters et al., 1995, J. Pharmacol. Exp. Ther. 274, 783). In the present study, subchronic (7-day i.p.) administration of haloperidol (1 mg/kg) decreased the accumulation of aminopeptidase-derived fragments Tyr and Gly-Gly-Phe-Met on cortical and striatal slices. The accumulation of Tyr-Gly-Gly, however, was not altered by haloperidol treatment on slices from either region. Further, aminopeptidase N activity was decreased in P2 membranes isolated from either the cortex or striatum of haloperidol-treated animals. These data suggest that the haloperidol-induced decrease in [Met5]enkephalin metabolism results, at least in part, from a reduction in the activity of aminopeptidase N.
Konkoy
C S
CS
Department of Pharmacology, University of Arizona Health Sciences Center, Tucson 85724, USA.
Waters
S M
SM
Davis
T P
TP
D000595:Amino Acid Sequence; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D018826:CD13 Antigens / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003864:Depression, Chemical; D004744:Enkephalin, Methionine / Q000378:metabolism*; D006220:Haloperidol / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008969:Molecular Sequence Data; D017072:Neostriatum / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D014150:Antipsychotic Agents; D010455:Peptides; D004744:Enkephalin, Methionine; D018826:CD13 Antigens; D006220:Haloperidol