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Beta 3‐adrenoceptor in rat aorta: molecular and biochemical characterization and signalling pathway
Author(s) -
Rautureau Yohann,
Toumaniantz Gilles,
Serpillon Sabrina,
Jourdon Philippe,
Trochu JeanNoël,
Gauthier Chantal
Publication year - 2002
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704867
Subject(s) - phenylephrine , endocrinology , medicine , agonist , aorta , endothelium , beta (programming language) , chemistry , stimulation , biology , receptor , blood pressure , computer science , programming language
We have previously demonstrated that β 3 ‐adrenoceptor (β 3 ‐AR) stimulation induces endothelium‐dependent vasorelaxation in rat aorta through the activation of an endothelial NO synthase associated with an increase in intracellular cGMP. The aim of the present study was to localise β 3 ‐AR to confirm our functional study and to complete the signalling pathway of β 3 ‐AR in rat aorta. By RT–PCR, we have detected β 3 ‐AR transcripts both in aorta and in freshly isolated endothelial cells. The absence of markers for adipsin or hormone‐sensitive lipase in endothelial cells excluded the presence of β 3 ‐AR from adipocytes. The localization of β 3 ‐AR in aortic endothelial cells was confirmed by immunohistochemistry using a rat β 3 ‐AR antibody. To identify the G protein linked to β 3 ‐AR, experiments were performed in rat pre‐treated with PTX (10 μg kg −1 ), a G i/0 protein inhibitor. The blockage of G i/0 protein by PTX was confirmed by the reduction of vasorelaxation induced by UK 14304, a selective α 2 ‐AR agonist. The cumulative concentration‐response curve for SR 58611A, a β 3 ‐AR agonist, was not significantly modified on aorta rings from PTX pre‐treated rats. At the same level of contraction, the relaxations induced by 10 μ M SR 58611A were significantly reduced in 30 m M ‐KCl pre‐constricted rings (E max =16.7±8.4%, n =5), in comparison to phenylephrine (0.3 μ M ) pre‐constricted rings (E max =49.11±11.0%, n =5, P <0.05). In addition, iberotoxin (0.1 μ M ), glibenclamide (1 μ M ) and 4‐aminopyridine (1 m M ), selective potassium channels blockers of K Ca , K ATP , and K v respectively, decreased the SR 58611A‐mediated relaxation. We conclude that β 3 ‐AR is preferentially expressed in rat aortic endothelial cells. β 3 ‐AR‐mediated aortic relaxation is independent of G i/0 proteins stimulation, but results from the activation of several potassium channels, K Ca , K ATP , and K v .British Journal of Pharmacology (2002) 137 , 153–161. doi: 10.1038/sj.bjp.0704867