Haloperidol and apomorphine differentially affect neuropeptidase activity

Stephen M. Waters, Christopher S. Konkoy, Thomas P Davis

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

In addition to their well characterized effects at dopamine receptors, neuroleptic drugs have been shown to affect the level and in vitro metabolism of neuropeptides. In the present study, the effect of acute and subchronic administration of the neuroleptic haloperidol and the nonselective, dopamine agonist apomorphine on neuropeptidase activity was determined in regional, rat brain P2 membranes. Subchronic administration of haloperidol decreased the activity of aminopeptidase N in the frontal codex and caudate-putamen. In contrast, subchronic administration of apomorphine increased aminopeptidase N activity in the frontal cortex and caudate-putamen. Neutral endopeptidase 24.11 also was affected differentially in the caudate-putamen, but both subchronic haloperidol and apomorphine decreased neutral endopeptidase 24.11 activity in the frontal codex. Metalloendopeptidase 24.15 activity was decreased in the caudate-putamen after acute haloperidol and increased in the frontal cortex after acute apomorphine administration; however, no effect was noted after subchronic administration of either drug. Angiotensin converting enzyme was not affected by any treatment. Therefore, neuroleptic-induced alterations in aminopeptidase N, neutral endopeptidase 24.11 and metalloendopeptidase 24.15 activity may account for previously reported alterations in neuropeptide degradation. In view of the interaction between mesocorticolimbic dopamine neurons and neuropeptides, e.g., substance P, neurotensin and enkephalins, neuroleptic-induced alterations in the activities of neuropeptidases, end thus neuropeptide metabolism can, in turn, play a role in modulating midbrain dopaminergic activity.

Original languageEnglish (US)
Pages (from-to)113-120
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume277
Issue number1
StatePublished - Apr 1996

Fingerprint

thimet oligopeptidase
Apomorphine
Putamen
Haloperidol
Neuropeptides
CD13 Antigens
Neprilysin
Antipsychotic Agents
Frontal Lobe
Neurotensin
Enkephalins
Dopaminergic Neurons
Dopamine Agonists
Dopamine Receptors
Peptidyl-Dipeptidase A
Substance P
Mesencephalon
Membranes
Brain
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Pharmacology

Cite this

Haloperidol and apomorphine differentially affect neuropeptidase activity. / Waters, Stephen M.; Konkoy, Christopher S.; Davis, Thomas P.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 277, No. 1, 04.1996, p. 113-120.

Research output: Contribution to journalArticle

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