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Rautureau Y, Toumaniantz G, Serpillon S, Jourdon P, Trochu JN, Gauthier C: Beta 3-adrenoceptor in rat aorta: molecular and biochemical characterization and signalling pathway. Br J Pharmacol. 2002 Sep;137(2):153-61.
1. We have previously demonstrated that beta (3)-adrenoceptor (beta (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 beta (3)-AR to confirm our functional study and to complete the signalling pathway of beta (3)-AR in rat aorta. 2. By RT-PCR, we have detected beta (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 beta (3)-AR from adipocytes. The localization of beta (3)-AR in aortic endothelial cells was confirmed by immunohistochemistry using a rat beta (3)-AR antibody. 3. To identify the G protein linked to beta (3)-AR, experiments were performed in rat pre-treated with PTX (10 microg 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 alpha (2)-AR agonist. The cumulative concentration-response curve for SR 58611A, a beta (3)-AR agonist, was not significantly modified on aorta rings from PTX pre-treated rats. 4. At the same level of contraction, the relaxations induced by 10 microM SR 58611A were significantly reduced in 30 mM-KCl pre-constricted rings (E (max)=16.7+/-8.4%, n=5), in comparison to phenylephrine (0.3 microM) pre-constricted rings (E (max)=49.11+/-11.0%, n=5, P <0.05). In addition, iberotoxin (0.1 microM), glibenclamide (1 microM) and 4-aminopyridine (1 mM), selective potassium channels blockers of K (Ca), K (ATP), and K (v) respectively, decreased the SR 58611A-mediated relaxation. 5. We conclude that beta (3)-AR is preferentially expressed in rat aortic endothelial cells. Beta (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). |
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