| First Author | Nagano K | Year | 2019 |
| Journal | J Biochem | Volume | 166 |
| Issue | 5 | Pages | 383-392 |
| PubMed ID | 31504625 | Mgi Jnum | J:291756 |
| Mgi Id | MGI:6435545 | Doi | 10.1093/jb/mvz071 |
| Citation | Nagano K, et al. (2019) Cooperative action of APJ and alpha1A-adrenergic receptor in vascular smooth muscle cells induces vasoconstriction. J Biochem 166(5):383-392 |
| abstractText | The apelin receptor (APJ), a receptor for apelin and elabela/apela, induces vasodilation and vasoconstriction in blood vessels. However, the prolonged effects of increased APJ-mediated signalling, involving vasoconstriction, in smooth muscle cells have not been fully characterized. Here, we investigated the vasoactive effects of APJ gain of function under the control of the smooth muscle actin (SMA) gene promoter in mice. Transgenic overexpression of APJ (SMA-APJ) conferred sensitivity to blood pressure and vascular contraction induced by apelin administration in vivo. Interestingly, ex vivo experiments showed that apelin markedly increased the vasoconstriction of isolated aorta induced by noradrenaline (NA), an agonist for alpha- and beta-adrenergic receptors, or phenylephrine, a specific agonist for alpha1-adrenergic receptor (alpha1-AR). In addition, intracellular calcium influx was augmented by apelin with NA in HEK293T cells expressing APJ and alpha1A-AR. To examine the cooperative action of APJ and alpha1A-AR in the regulation of vasoconstriction, we developed alpha1A-AR deficient mice using a genome-editing technique, and then established SMA-APJ/alpha1A-AR-KO mice. In the latter mouse line, aortic vasoconstriction induced by a specific agonist for alpha1A-AR, A-61603, were significantly less than in SMA-APJ mice. These results suggest that the APJ-enhanced response requires alpha1A-AR to contract vessels coordinately. |
