Document Detail


Secretin and VIP-stimulated adenylate cyclase from rat heart. I. General properties and structural requirements for enzyme activation.
MedLine Citation:
PMID:  7193463     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Membrane adenylate cyclase from rat heart was activated by the two gut peptides secretin and vasoactive intestinal peptide (VIP), glucagon, and the beta-adrenergic drug isoproterenol, in the presence of guanosine 5'-triphosphate (GTP). With all the stimuli tested, the optimal magnesium concentration was 5 mM, i.e. in excess over the 0.5 mM ATP substrate concentration and 0.01 mM GTP used as cofactor. Under these conditions, half-maximal adenylate cyclase activation with glucagon, secretin, and VIP was achieved at concentrations of 0.5, 0.5 and 1.0 microM, respectively. Data obtained with the secretin (7--27) fragment, a secretin antagonist, indicate that secretin and VIP acted on the same binding sites, which differed from glucagon binding sites. Structural requirements for secretin activation of cardiac adenylate cyclase were evaluated by comparing the potency and efficacy of parent peptides and synthetic analogs. The gastric inhibitory peptide GIP was inactive. When using 13 mono-or bi-substituted analogs, it appeared that amino acids in positions 1, 2, 3, 4 and 6 were of major importance while those in position 5 and 11 played a relatively minor role.
Authors:
P Chatelain; P Robberecht; P De Neef; M Deschodt-Lanckman; W König; J Christophe
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Pflügers Archiv : European journal of physiology     Volume:  389     ISSN:  0031-6768     ISO Abbreviation:  Pflugers Arch.     Publication Date:  1980 Dec 
Date Detail:
Created Date:  1981-05-28     Completed Date:  1981-05-28     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0154720     Medline TA:  Pflugers Arch     Country:  GERMANY, WEST    
Other Details:
Languages:  eng     Pagination:  21-7     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate
Adenylate Cyclase / metabolism*
Animals
Dose-Response Relationship, Drug
Enzyme Activation
Gastrointestinal Hormones / pharmacology*
Glucagon / pharmacology
Guanosine Triphosphate
Isoproterenol / pharmacology
Magnesium / pharmacology
Male
Myocardium / enzymology*
Rats
Secretin / pharmacology*
Structure-Activity Relationship
Vasoactive Intestinal Peptide / pharmacology*
Grant Support
ID/Acronym/Agency:
R0-IAM-17010/AM/NIADDK NIH HHS
Chemical
Reg. No./Substance:
0/Gastrointestinal Hormones; 1393-25-5/Secretin; 37221-79-7/Vasoactive Intestinal Peptide; 56-65-5/Adenosine Triphosphate; 7439-95-4/Magnesium; 7683-59-2/Isoproterenol; 86-01-1/Guanosine Triphosphate; 9007-92-5/Glucagon; EC 4.6.1.1/Adenylate Cyclase

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


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