Document Detail


Pharmacological studies of neurotensin, several fragments and analogous in the isolated perfused rat heart.
MedLine Citation:
PMID:  7418719     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Neurotensin (NT) induced a dose-dependent increase of the coronary perfusion pressure (CPP) in the isolated perfused rat heart. This effect was not modified by pretreating the organ with methysergide (8.5 x 10(-6) M), atropine (3.4 x 10(-6) M), a mixture of phentolamine (3.1 x 10(-6) M) and practolol (1.5 x 10(-5) M), 8-leucine-angiomine (2.9 x 10(-5) M) thus suggesting the existence of specific NT receptors in the coronary vessels of rat. The structure-activity studies performed using several NT fragments and analogues in the isolated perfused rat heart led us to the following conclusions: (1) the minimum structure required for the full expression of the biological activity of NT is H-Arg9-Pro10-Tyr11-Ile12-Leu13-OH; (2) the amino acid Tyr in position 11 appears to play a key role in the process of NT receptor activation. The replacement of Tyr11 with Tyr(Me) gave a compound which inhibits selectively the increase in coronary perfusion pressure induced by NT, but still exhibits some NT-like activity, specially when used in concentrations higher than 10(-6) M. [Tyr(Me)11]NT did not antagonize the stimulant effects of NT in rat stomach strips and guinea pig atria, thus suggesting that the receptors mediating the constrictor effect of NT in coronary vessels of the rat are pharmacologically different from those subserving the stimulant effect of NT in rat stomach strip and guinea pig atria.
Authors:
R Quirion; F Rioux; D Regoli; S St-Pierre
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of pharmacology     Volume:  66     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  1980 Sep 
Date Detail:
Created Date:  1980-12-16     Completed Date:  1980-12-16     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  257-66     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Pressure / drug effects
Coronary Circulation / drug effects
Drug Interactions
Female
Heart / drug effects*
Male
Neurotensin / analogs & derivatives*,  pharmacology*
Peptide Fragments / pharmacology
Rats
Structure-Activity Relationship
Chemical
Reg. No./Substance:
0/Peptide Fragments; 39379-15-2/Neurotensin

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


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