Enzyme Kinetic Studies and Inhibition by Oligopeptides of LH-RH Degradation in Rat Hypothalamus and Pituitary

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Abstract

The enzyme kinetic parameters of the degradation of luteinizing hormone-releasing hormone (LH-RH) and L-cystine-bis-(4-nitroanilide) (Cys-NA) by rat hypothalamic (HYP) and pituitary (PIT) extracts and the effect of various oligopeptides on the rate of LH-RH inactivation were investigated in vitro. The 105,000 × g supernatant of 1 rat HYP inactivated 57 μg LH-RH during a 30 min incubation (Km = 12.4 μM,Vmax = 2.33 μg LH-RH/mg protein/min), and of one rat anterior PIT, 48 μg LH-RH during 30 min of incubation (Km = 12.2 μM, Vmax = 8.0 μg LH-RH/mg protein/min). The synthetic substrate Cys-NA competitively inhibited LH-RH degradation with a Ki of 8.5 μM in the HYP and 6 μM in the PIT enzyme preparation. Vice versa, LH-RH also competitively inhibited the cleavage of Cys-NA with inhibition constants of 14 μM (HYP) and 15 μM (PIT) indicating that the 2 substrates are probably cleaved by the same enzyme. The most effective inhibitors of LH-RH degradation were found to be angiotensin-related peptides, neurotensin, bradykinin, and bacitracin. A relatively weak effect was obtained with oxytocin, enkephalin and puromycin. It is concluded that endogenous oligopeptides such as angiotensins, neurotensin, bradykinin, etc., may possibly influence LH-RH degradation in the PIT and the HYP. The synthetic substrate Cys-NA may be an appropriate substrate for measuring the activity of an LH-RH-degrading peptidase, which therefore could be classified as arylamidase.

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Author and article information

Journal

Journal ID (publisher-id): NEN

Journal ID (nlm-ta): Neuroendocrinology

Journal ID (doi): 10.1159/issn.0028-3835

Title: Neuroendocrinology

Publisher: S. Karger AG

ISSN (Print): 0028-3835

ISSN (Electronic): 1423-0194

Publication date Subscription-year: 1979

Publication date (Print): 1979

Publication date (Electronic): 26 March 2008

Volume: 28

Issue: 5

Pages: 339-348

Affiliations

Division of gynecologic Endocrinology, Department of Obstetrics and Gynecology, Johann Wolfgang Goethe University, and Hoechst AG, Pharmacology H 821, Frankfurt am Main

Article

Publisher ID: 122881 Other ID: Neuroendocrinology 1979;28:339–348

DOI: 10.1159/000122881

PubMed ID: 375117

SO-VID: a75d02c1-ca17-44aa-9e1a-111896ac936d

License:

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

History

Date received : 08 August 1978

Date accepted : 06 November 1978

Page count

Pages: 10

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