Document Detail

Peptidase modulation of the pulmonary effects of tachykinins in tracheal superfused guinea pig lungs.
MedLine Citation:
PMID:  1688568     Owner:  NLM     Status:  MEDLINE    
The effects of the angiotensin converting enzyme (ACE) inhibitor captopril and the neutral endopeptidase (NEP) inhibitors thiorphan and SCH 32615 on the changes in airway opening pressure (PaO) and the recovery of offered peptide were studied after intratracheal administration of substance P (SP) and neurokinin A (NKA) in isolated guinea pig lungs superfused through the trachea. Pao changes and the recovery of offered peptide were significantly greater in NEP inhibitor-treated lungs than in control lungs. Captopril did not cause a significant change in the physiological effects or the recovery of SP and NKA. HPLC analysis of [3H]Pro2,4-SP and 125I-Histidyl1-NKA perfused through the airways showed major cleavage products consistent with NEP action. We conclude that there is significant degradation of both SP and NKA after tracheal infusion of peptides by NEP-like but not by ACE activity; this effect significantly influences the physiological effects of these peptides.
M A Martins; S A Shore; N P Gerard; C Gerard; J M Drazen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  85     ISSN:  0021-9738     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  1990 Jan 
Date Detail:
Created Date:  1990-02-14     Completed Date:  1990-02-14     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  170-6     Citation Subset:  AIM; IM    
Ina Sue Permultter Laboratory, Children's Hospital, Boston, Massachusetts.
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MeSH Terms
Captopril / pharmacology
Dipeptides / pharmacology
Guinea Pigs
Lung / drug effects,  physiology*
Neurokinin A / metabolism,  pharmacology*
Peptide Hydrolases
Substance P / metabolism,  pharmacology*
Thiorphan / pharmacology
Trachea / physiology*
Grant Support
Reg. No./Substance:
0/Dipeptides; 33507-63-0/Substance P; 62571-86-2/Captopril; 76721-89-6/Thiorphan; 83861-02-3/SCH 32615; 86933-74-6/Neurokinin A; EC 3.4.-/Peptide Hydrolases

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