Action of three ectopeptidases on corticotropin-releasing factor

metabolism and functional aspects.

James C. Ritchie, Thomas P. Davis, Charles Nemeroff

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Using purified enzyme preparations, we investigated the actions of angiotensin-converting enzyme, aminopeptidase N, and endopeptidase 24.11 on corticotropin-releasing factor (CRF). The effects of inhibition of these enzymes on CRF action in rat anterior pituitary cultures were also determined. Finally, specific inhibitors were used to evaluate ectopeptidase action on the regional brain metabolism of CRF. K(m) values for CRF were 165, 90, and 42 microM for angiotensin-converting enzyme, aminopeptidase N, and endopeptidase 24.11, respectively. A CRF metabolite profile for each enzyme was determined. In pituitary cultures, inhibition of endopeptidase 24.11 and aminopeptidase N potentiated CRF-stimulated release of adrenocorticotropic hormone (ACTH). In rat pituitary and hypothalamus membrane preparations, specific inhibitor experiments indicated that CRF hydrolysis involved members of the neutral endopeptidase and aminopeptidase enzyme families. In cortex membranes, similar peptidase inhibition was without effect. These data support the hypothesis that ectopeptidases play a major role in CRF metabolism and biological function.

Original languageEnglish
Pages (from-to)22-33
Number of pages12
JournalNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
Volume28
Issue number1
StatePublished - Jan 1 2003
Externally publishedYes

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Corticotropin-Releasing Hormone
Neprilysin
CD13 Antigens
Peptidyl-Dipeptidase A
Enzymes
Aminopeptidases
Membranes
Adrenocorticotropic Hormone
Hypothalamus
Hydrolysis
Peptide Hydrolases
Brain

ASJC Scopus subject areas

  • Pharmacology

Cite this

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