Document Detail


Pharmacological characterization of nucleotide P2Y receptors on endothelial cells of the mouse aorta.
MedLine Citation:
PMID:  15997227     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Nucleotides regulate various effects including vascular tone. This study was aimed to characterize P2Y receptors on endothelial cells of the aorta of C57BL6 mice. Five adjacent segments (width 2 mm) of the thoracic aorta were mounted in organ baths to measure isometric force development. Nucleotides evoked complete (adenosine 5' triphosphate (ATP), uridine 5' triphosphate (UTP), uridine 5' diphosphate (UDP); >90%) or partial (adenosine 5' diphosphate (ADP)) relaxation of phenylephrine precontracted thoracic aortic rings of C57BL6 mice. Relaxation was abolished by removal of the endothelium and was strongly suppressed (>90%) by inhibitors of nitric oxide synthesis. The rank order of potency was: UDP approximately UTP approximately ADP>adenosine 5'-[gamma-thio] triphosphate (ATPgammaS)>ATP, with respective pD2 values of 6.31, 6.24, 6.22, 5.82 and 5.40. These results are compatible with the presence of P2Y1 (ADP>ATP), P2Y2 or P2Y4 (ATP and UTP) and P2Y6 (UDP) receptors. P2Y4 receptors were not involved, since P2Y4-deficient mice displayed unaltered responses to ATP and UTP. The purinergic receptor antagonist suramin exerted surmountable antagonism for all agonists. Its apparent pKb for ATP (4.53+/-0.07) was compatible with literature, but the pKb for UTP (5.19+/-0.03) was significantly higher. This discrepancy suggests that UTP activates supplementary non-P2Y2 receptor subtype(s). Further, pyridoxal-phosphate-6-azophenyl-2'-4'-disulphonic acid (PPADS) showed surmountable (UTP, UDP), nonsurmountable (ADP) or no antagonism (ATP). Finally, 2'-deoxy-N6-methyladenosine3',5'-bisphosphate (MRS2179) inhibited ADP-evoked relaxation only. Taken together, these results point to the presence of functional P2Y1 (ADP), P2Y2 (ATP, UTP) and P2Y6 (UDP) receptors on murine aorta endothelial cells. The identity of the receptor(s) mediating the action of UTP is not fully clear and other P2Y subtypes might be involved in UTP-evoked vasodilatation.
Authors:
Pieter-Jan D F Guns; András Korda; Herta M Crauwels; Tim Van Assche; Bernard Robaye; Jean-Marie Boeynaems; Hidde Bult
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of pharmacology     Volume:  146     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2005 Sep 
Date Detail:
Created Date:  2005-09-15     Completed Date:  2005-12-09     Revised Date:  2010-09-20    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  288-95     Citation Subset:  IM    
Affiliation:
Division of Pharmacology, University of Antwerp, 2610 Wilrijk, Belgium. pieter-jan.guns@ua.ac.be
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MeSH Terms
Descriptor/Qualifier:
Animals
Aorta, Thoracic / cytology,  drug effects*
Binding, Competitive / drug effects
Dose-Response Relationship, Drug
Endothelial Cells / drug effects*
Mice
Mice, Inbred C57BL
Mice, Knockout
Muscle Contraction / drug effects
Muscle Relaxation / drug effects
Muscle, Smooth, Vascular / cytology,  drug effects*
Nucleotides / pharmacology
Receptors, Purinergic P2 / agonists,  antagonists & inhibitors,  drug effects*,  genetics,  physiology
Vasodilator Agents / pharmacology
Chemical
Reg. No./Substance:
0/Nucleotides; 0/Receptors, Purinergic P2; 0/Vasodilator Agents; 0/purinoceptor P2Y4
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