![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
A Lasdun, S Reznik, CJ Molineaux and M Orlowski
Department of Pharmacology, Mount Sinai School of Medicine, City University of New York.
Endopeptidase (EP) 24.15 cleaves the Tyr5-Gly6 bond of luteinizing hormone-releasing hormone (LHRH) (pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro- Gly-NH2), and is the primary LHRH degrading enzyme in pituitary and hypothalamic membrane preparations. Potent and specific inhibitors were used to identify the enzymes involved in the in vivo degradation of LHRH. After i.c.v. administration of LHRH, only about 1% of the peptide was recovered from brain after 1 hr. Concurrent administration of LHRH and N-[1-(RS)-carboxy-3-phenylpropyl]-Ala-Ala-Phe-p-aminobenzoate (cFP- AAF-pAB), a specific inhibitor of EP 24.15, led to a more than 10-fold increase in LHRH recovery. Administration of N-[1-(RS)-carboxy-3- phenylpropyl]-Phe-pAB (cFP-F-pAB) or captopril, inhibitors of "enkephalinase" (EP 24.11) and angiotensin converting enzyme, respectively, did not significantly increase LHRH recovery. Intravenous administration of LHRH and either cFP-F-pAB or cFP-AAF-pAB but not captopril, led to an increase in the half-life of LHRH from 10 min to 15 and 20 min, respectively. Concurrent administration of both inhibitors resulted in a dramatic 8-fold increase in the half-life of LHRH, similar to values reported for "superactive" analogs of LHRH which are rendered resistant to enzymatic degradation by introduction of a D-amino acid in position 6. Concentrations of plasma LHRH 65 to 80 min after administration of inhibitors were 100- to 200-fold higher than those in controls. The potentiating effect of cFP-F-pAB resulted from inhibition of the in vivo degradation of cFP-AAF-pAB by EP 24.11.(ABSTRACT TRUNCATED AT 250 WORDS)
This article has been cited by other articles:
|
|
 |
|
  K. Walters, I. N. Wegorzewska, Y.-P. Chin, M. G. Parikh, and T. J. Wu Luteinizing Hormone-Releasing Hormone I (LHRH-I) and Its Metabolite in Peripheral Tissues Experimental Biology and Medicine, February 1, 2008; 233(2): 123 - 130. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. N. Shrimpton, A. I. Smith, and R. A. Lew Soluble Metalloendopeptidases and Neuroendocrine Signaling Endocr. Rev., October 1, 2002; 23(5): 647 - 664. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Yamanaka, M. C. Lebrethon, E. Vandersmissen, A. Gerard, G. Purnelle, M. LeMaitre, S. Wilk, and J. P. Bourguignon Early Prepubertal Ontogeny of Pulsatile Gonadotropin-Releasing Hormone (GnRH) Secretion: I. Inhibitory Autofeedback Control through Prolyl Endopeptidase Degradation of GnRH Endocrinology, October 1, 1999; 140(10): 4609 - 4615. [Abstract] [Full Text]
|
|
|
|
 |
|
 P. M. Cummins, A. Pabon, E. H. Margulies, and M. J. Glucksman Zinc Coordination and Substrate Catalysis within the Neuropeptide Processing Enzyme Endopeptidase EC 3.4.24.15. IDENTIFICATION OF ACTIVE SITE HISTIDINE AND GLUTAMATE RESIDUES J. Biol. Chem., June 4, 1999; 274(23): 16003 - 16009. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. S. Saphire, S. J. Bark, and L. Gerace All Four Homochiral Enantiomers of a Nuclear Localization Sequence Derived from c-Myc Serve as Functional Import Signals J. Biol. Chem., November 6, 1998; 273(45): 29764 - 29769. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Herbison Multimodal Influence of Estrogen upon Gonadotropin-Releasing Hormone Neurons Endocr. Rev., June 1, 1998; 19(3): 302 - 330. [Abstract] [Full Text]
|
|
|
|
|
|
J. Jirácek, A. Yiotakis, B. Vincent, A. Lecoq, A. Nicolaou, F.édér. Checler, and V. Dive Development of Highly Potent and Selective Phosphinic Peptide Inhibitors of Zinc Endopeptidase 24-15 Using Combinatorial Chemistry J. Biol. Chem., September 15, 1995; 270(37): 21701 - 21706. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Tullai, P. M. Cummins, A. Pabon, J. L. Roberts, M. C. Lopingco, C. N. Shrimpton, A. I. Smith, J. A. Martignetti, E. S. Ferro, and M. J. Glucksman The Neuropeptide Processing Enzyme EC 3.4.24.15 Is Modulated by Protein Kinase A Phosphorylation J. Biol. Chem., November 17, 2000; 275(47): 36514 - 36522. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
