Reference : Lack of involvement of pertussis toxin-sensitive G-proteins in norepinephrine-induced...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/10993/5720
Lack of involvement of pertussis toxin-sensitive G-proteins in norepinephrine-induced vasoconstriction of rat aorta smooth muscle
English
Petitcolin, M. A. [> >]
Vandeputte, C. [> >]
Spitzbarth-Régrigny, E. [> >]
Bueb, Jean-Luc mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Capdeville-Atkinson, C. [> >]
Tschirhart, Eric mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
2001
Biochemical Pharmacology
Elsevier Science
61
4
485-91
Yes (verified by ORBilu)
0006-2952
Oxford
United Kingdom
[en] isolation & purification ; Pertussis Toxin ; Norepinephrine ; Muscle, Smooth, Vascular ; Male ; Heterotrimeric GTP-Binding Proteins ; GTP-Binding Protein alpha Subunits, Gi-Go ; GTP Phosphohydrolases ; Enzyme Activation ; Dose-Response Relationship, Drug ; Aorta ; Animals ; Prazosin ; Radioligand Assay ; metabolism ; physiology ; drug effects ; pharmacology ; Virulence Factors, Bordetella ; Vasoconstriction ; Tritium ; Receptors, Adrenergic, alpha-1 ; Receptors, Adrenergic ; Rats, Wistar ; Rats ; Adrenergic alpha-Agonists
[en] Several studies have shown that stimulation of pertussis toxin (PTX)-sensitive G-proteins amplified alpha-adrenoceptor (alpha-AR) agonist-induced vasoconstriction in small muscular and resistance arteries. The aim of this study was to assess the potential involvement of PTX-sensitive G-proteins in norepinephrine (NE)-induced constriction in a large diameter artery, the rat aorta. PTX (1 microg/mL, 2 hr; 3 microg/mL, 4 hr) did not modify concentration-response curves to NE in endothelium-denuded aortic rings. However, several lines of evidence suggested that aortic smooth muscle cells (SMC) had a PTX-sensitive G-protein pathway. [alpha-(32)P]ADP-ribosylation of G(i/o)-proteins by PTX (3 microg/mL, 4 hr) was demonstrated in situ in the intact aorta without endothelium. alpha(i/o) subunits were identified in vitro by both immunoblotting and ADP-ribosylation experiments in rat aorta SMC membranes. The measurement of G(i/o)-specific GTPase activity evidenced an effective coupling between NE receptors and G(i/o)-proteins, as NE induced an increase in basal G(i/o)-specific GTPase activity (20.7 +/- 2.8 vs 7.2 +/- 2.2 pmol P(i)/mg protein at 5 min; P < 0.05 vs basal). Co-immunoprecipitation revealed the in vitro coupling between alpha(1D)-ARs and G(i)-protein in rat aorta SMC membranes. In conclusion, we identified a PTX-sensitive G(i/o)-protein pathway in rat endothelium-denuded aorta. We showed an effective coupling between NE receptors and G(i)-proteins via alpha(1D)-ARs. Since PTX has no effect on NE-induced vasoconstriction, the PTX-sensitive G(i)-protein pathway does not play a predominant role in NE-induced responses in rat aorta SMC in contrast to small diameter muscular and resistance arteries.
http://hdl.handle.net/10993/5720

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