Document Detail


1-O-alkyl-2-N-methylcarbamyl-glycerophosphocholine: a biologically potent, non-metabolizable analog of platelet-activating factor.
MedLine Citation:
PMID:  2820395     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We prepared unlabeled and 3H-labeled analogs of platelet-activating factor (PAF) containing a N-methylcarbamyl residue at the sn-2 position. PAF and its methylcarbamyl analog competed for binding to high affinity receptors on human polymorphonuclear neutrophils; their respective dissociation constants for these receptors were 0.2 and 1.1 nM. The binding affinities of the two analogs correlated precisely with their capacities to stimulate neutrophil degranulation responses. Unlike PAF, however, the methylcarbamyl analog completely resisted metabolic inactivation by neutrophils and by human sera. Thus, these compounds' biological potencies are determined predominantly by receptor binding: cellular metabolism of the ligands neither contributes to nor appreciably limits their stimulating actions.
Authors:
J T O'Flaherty; J F Redman; J D Schmitt; J M Ellis; J R Surles; M H Marx; C Piantadosi; R L Wykle
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  147     ISSN:  0006-291X     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  1987 Aug 
Date Detail:
Created Date:  1987-10-08     Completed Date:  1987-10-08     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  18-24     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
1-Alkyl-2-acetylglycerophosphocholine Esterase
Leukotriene B4 / pharmacology
Neutrophils / drug effects,  metabolism
Phospholipases A / metabolism
Phospholipid Ethers*
Platelet Activating Factor / analogs & derivatives*,  pharmacology
Platelet Membrane Glycoproteins*
Receptors, Cell Surface / metabolism
Receptors, G-Protein-Coupled*
Stereoisomerism
Structure-Activity Relationship
Grant Support
ID/Acronym/Agency:
HL-26257/HL/NHLBI NIH HHS; HL-26818/HL/NHLBI NIH HHS; HL-27799/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Phospholipid Ethers; 0/Platelet Activating Factor; 0/Platelet Membrane Glycoproteins; 0/Receptors, Cell Surface; 0/Receptors, G-Protein-Coupled; 0/platelet activating factor receptor; 111057-91-1/1-O-hexadecyl-2-N-methylcarbamylphosphatidylcholine; 71160-24-2/Leukotriene B4; EC 3.1.1.-/Phospholipases A; EC 3.1.1.47/1-Alkyl-2-acetylglycerophosphocholine Esterase

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


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