Document Detail


ACE-like hydrolysis of gastrin analogs and CCK-8 by fundic mucosal cells of different species with release of the amidated C-terminal dipeptide.
MedLine Citation:
PMID:  2163679     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Various gastrin analogues and CCK-8 (Asp-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-Phe-NH2) are hydrolyzed in vitro by angiotensin-converting enzyme (ACE), the main and initial cleavage occurring at the Met-Asp (or Leu-Asp) bond, releasing the C-terminal dipeptide amide Asp-Phe-NH2. Tetragastrin analogues (e.g., Boc-Trp-Leu-Asp-Phe-NH2) are degraded by a vesicular membrane fraction from rat gastric mucosa, yielding the C-terminal dipeptide Asp-Phe-NH2. We report here on the degradation of gastrin analogues and CCK-8 by a gastric mucosal cell preparation containing specific gastrin receptors. We have shown that gastrin analogues were specifically degraded by gastric mucosal cells from different species (e.g., rabbit and dog) at 37 degrees C (pH 7.4), releasing the C-terminal dipeptide Asp-Phe-NH2, similarly to ACE. This cleavage was found to be temperature and pH sensitive, and was inhibited by metalloproteinase inhibitors and by captopril, strongly suggesting that this enzymatic system closely resembles ACE. We have also demonstrated that a close correlation seems to exist between the apparent affinity of the gastrin analogues for gastrin receptors on gastric mucosal cells, and their ability of being hydrolyzed by this cell preparation. Moreover, all gastrin analogues which have been demonstrated to act as gastrin antagonists remained unaffected in the incubation conditions.
Authors:
P Dubreuil; P Fulcrand; M Rodriguez; J Laur; J P Bali; J Martinez
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1039     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  1990 Jun 
Date Detail:
Created Date:  1990-08-13     Completed Date:  1990-08-13     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  171-6     Citation Subset:  IM    
Affiliation:
Centre CNRS-INSERM de Pharmacologie-Endocrinologie, Montpellier, France.
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MeSH Terms
Descriptor/Qualifier:
Amides / metabolism
Amino Acid Sequence
Animals
Cells, Cultured
Dipeptides / isolation & purification,  metabolism
Dogs
Gastric Fundus
Gastric Mucosa / metabolism*
Gastrins / metabolism*
Hydrolysis
Kinetics
Molecular Sequence Data
Peptidyl-Dipeptidase A / metabolism*
Rabbits
Sincalide / metabolism*
Species Specificity
Substrate Specificity
Chemical
Reg. No./Substance:
0/Amides; 0/Dipeptides; 0/Gastrins; 25126-32-3/Sincalide; EC 3.4.15.1/Peptidyl-Dipeptidase A

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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